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The Role of Cytokines in Hematolymphoid Development

  • Chapter
Molecular Biology of B-Cell and T-Cell Development

Part of the book series: Contemporary Immunology ((CONTIM))

Abstract

For an uncommitted mesodermally derived stem cell to develop into a functionally mature blood cell, it must be capable of proliferation, commitment, differentiation, survival, and homing. These complex processes are tightly regulated by signals derived from the cells that make up the microenvironment in which hematopoiesis takes place. These include a variety of cell types, both nonhematopoietic fixed-tissue cells such as fibroblasts and epithelial cells (collectively referred to as “stromal cells”), and hematopoietic cells themselves. These cells influence hematopoiesis in three major ways: by providing signals through direct cell—cell contact, by secreting components of the extra-cellular matrix (ECM), and, by secreting soluble factors. Together, these signals comprise the hematopoietic inductive microenvironment or HIM (1). Microenvironments within different hematopoietic tissues are distinct and specialized in supporting the development of specific hematopoietic cell populations. For example, the thymus that almost exclusively supports T-cell development consists of a separate class of epithelial cells, bone marrow-derived cells, and cytokines that are different from that in the bone marrow, which supports the development of myeloid, erythroid, and B-cells. The intriguing observation that precursor cells from the thymus, when injected into recipient mice (2), or cultured in vitro with bone marrow stromal cells (3), can give rise to B-cells and/ or macrophages, exemplifies the inductive nature of hematopoietic microenvironments and demonstrates the ability of different sites to support the generation of distinct hematopoietic cell lineages.

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References

  1. Trentin, J. J. (1970) Influence of hematopoietic organ stroma (hemopoietic microenvironment) on stem cell differentiation, in Regulation of Hematopoiesis ( Gordon, A. S., ed.), Meredith, New York, pp. 161–186.

    Google Scholar 

  2. Wu, L. Antica, M., Johnson, G., Scollay, R., and Shortman, K. (1991) Developmental potential of the earliest precursor cells from the the adult mouse thymus. J. Exp. Med. 174 1617–1627.

    Article  CAS  PubMed  Google Scholar 

  3. Watson, J. D., Morrissey, P. J., Namen, A. E., Conlon, P. J., and Widmer, M. B. (1989) Effect of IL-7 on the growth of fetal thymocytes in culture. J. Immunol. 143, 1215–1222.

    CAS  PubMed  Google Scholar 

  4. Miller, M. D. and Krangel, M. S. (1992) Biology and biochemistry of the chemokines: A family of chemotactic and inflammatory cytokines. Crit. Rev. Immunol. 12, 17–46.

    CAS  PubMed  Google Scholar 

  5. Lorenzo, J. A. (1991) The role of cytokines in the regulation of local bone resorption. Crit. Rev. Immunol. 11, 195–213.

    CAS  PubMed  Google Scholar 

  6. Tabibzadeh, S. (1991) Human endometrium: an active site of cytokine production and action. Endocrine Rev. 12, 272–290.

    Article  CAS  Google Scholar 

  7. Bradley, T. R. and Metcalf, D. (1966) The growth of mouse bone marrow cells in vitro. Aust. J. Exp. Biol. Med. Sci. 44, 287–299.

    Article  CAS  PubMed  Google Scholar 

  8. Ichikawa, Y., Pluznik, D H, and Sachs, L. (1966) In vitro control of the development of macrophage and granulocyte colonies. Proc. Natl. Acad. Sci. USA 56, 488–495.

    Article  CAS  PubMed  Google Scholar 

  9. Smith, K. (1988) Interleukin 2, Inception, Impact, and implications. Science 240, 1169–1176.

    Article  CAS  PubMed  Google Scholar 

  10. Chen, B. D.-M. and Najor, F. (1987) Macrophage activation by interferon alpha and beta is associated with a loss of proliferative capacity: role of interferon alpha and beta in the regulation of macrophage proliferation and function. Cell. Immunol. 106, 343–354.

    Article  CAS  PubMed  Google Scholar 

  11. Moore, R. N., Larsen, H. S., Horohov, D. W., and Rouse, B. T. (1984) Endogenous regulation of macrophage proliferative expansion by colony stimulating factor-induced interferon. Science 223, 178–181.

    Google Scholar 

  12. Schultz, R. M. and Chirigos, M. A. (1978) Similarities among factors that render macrophages tumoricidal in lymphokine and interferon preparations. Cancer. Res. 38, 1003–1007.

    CAS  PubMed  Google Scholar 

  13. Kroemer, G., Andreu-Sanchex, J. L., Gonzalo, J. A., Gutierrez-Ramos, J. C., and Martinez-A, C. (1991) Interleukin-2, autotolerance, and autoimmunity Adv. Immunol. 50, 147–235.

    Article  CAS  PubMed  Google Scholar 

  14. Schluesener, H. J. and Lider, O. (1989) Transforming growth factors 01 and ß2: cytokines with identical immunosuppressive effects and a potential role in the regulation of autoimmune T cell function. J. Neuroimmunol. 24, 249–258.

    Article  CAS  PubMed  Google Scholar 

  15. Wahl, S. M., Allen, J. B., Wong, H. L., Dougherty, S. F., and Ellingsworth, L. R. (1990) Antagonistic and agonistic effects of transforming growth factor-13 and IL-1 in rheumatoid synovium. J. Immunol. 145, 2514–2519.

    CAS  PubMed  Google Scholar 

  16. Hoffman, R. (1989) Regulation of megakaryocytopoiesis. Blood 74, 1196–1212.

    CAS  PubMed  Google Scholar 

  17. Karray, S., deFrance, T., Merle-Béral, H., Banchereau, J., Debré, P., and Galanaud, P. (1988) Interleukin 4 counteracts the interleukin 2-induced proliferation of monoclonal B cells. J. Exp. Med. 168, 85–94.

    Article  CAS  PubMed  Google Scholar 

  18. Vellenga, E., de Wolfe, J. T. M., Beentjes, J. A. M., Esselink, M. T., Smit, J. W., and Halie, M. R. (1990) Divergent effects of interleukin-4 (IL-4) on the granulocyte colony-stimulating factor and IL-3-supported myeloid colony formation from normal and leukemic bone marrow cells. Blood 75, 633–637.

    CAS  PubMed  Google Scholar 

  19. Alegre, M.-L., Vandenabeele, P., Depierreuz, M., Florquin, S., Deschodt-Lanckman, M., Flamand, V., Moser, M., Leo, O., Urbain, J., Fiers, W., and Goldman, M. (1991) Cytokine release syndrome induced by the 145–2C11 anti-CD3 monoclonal antibody in mice: prevention by high doses of methylprednisone. J. Immunol. 146, 1184–1191.

    CAS  PubMed  Google Scholar 

  20. Gordon, M. Y., Riley, G. P., Watt, S. M., and Greaves, M. F. (1987) Compartmentalization of a haematopoietic growth factor (GM-CSF) by glycosaminoglycans in the bone marrow micro-environment. Nature 326, 403–405.

    Article  CAS  PubMed  Google Scholar 

  21. Li, Y.-S., Milner, P. G., Chauhan, A. K., Watson, M. A., Hoffman, R. M., Kodner, C. M., Milbrandt, J., and Deuel, T. F. (1990) Cloning and expression of a developmentally regulated protein that induces mitogenic and neurite outgrowth activity. Science 250, 1690–1692.

    Article  CAS  PubMed  Google Scholar 

  22. Merenmies, J. and Rauvala, H. (1990) Molecular cloning of the 18-kDa growth-associated protein of developing brain. J. Biol. Chem. 265, 16,721–16, 728.

    Google Scholar 

  23. Roberts, R., Gallagher, J., Spooncer, E., Allen, T. D., Bloomfield, F., and Dexter, T. M. (1988) Heparan sulfate bound growth factors: a mechanism for stromal cell mediated haemopoiesis. Nature 332, 376–378.

    Article  CAS  PubMed  Google Scholar 

  24. Kroemer, G., Cuende, E., and Martinez-A, C. (1993) Compartmentalization of the peripheral immune system. Adv. Immunol. 53, 157–216.

    Article  CAS  PubMed  Google Scholar 

  25. Kroemer, G., Toribio, M. L., and Martinez-A, C. (1991) Interleukin-2: counteracting pleiotropism by compartmentalization. New Biologist 3, 219–229.

    CAS  PubMed  Google Scholar 

  26. Oster, W., Lindemann, A., Mertelsmann, R., and Herrmann, F. (1989) Granulocyte-macrophage colony-stimulating factor (CSF) and multilineage CSF recruit human monocytes to express granulocyte CSF. Blood 73, 64–67.

    Google Scholar 

  27. Wieser, M., Bonifer, R., Oster, W., Lindemann, A., Mertelsmann, R., and Herrmann, F. (1989) Interleukin-4 induces secretion of CSF for granulocytes and CSF for macrophages by peripheral blood monocytes. Blood 73, 1105–1108.

    CAS  PubMed  Google Scholar 

  28. Horiguchi, J., Warren, M. K., and Kufe, D. (1987) Expression of the macrophage-specific colony-stimulating factor in human monocytes treated with granulocyte-macrophage colony-stimulating factor. Blood 69, 1259–1261.

    CAS  PubMed  Google Scholar 

  29. Pistoia, V., Ghio, R., Roncella, S., Cozzolino, F., Zupo, S., and Ferrarini, M. (1987) Production of colony-stimulating activity by normal and neoplastic human B lymphocytes. Blood 69, 1340–1347.

    CAS  PubMed  Google Scholar 

  30. Rambaldi, A., Young, D. C., and Griffin, J. D. (1987) Expression of the M-CSF (CSF-1) gene by human monocytes. Blood 69, 1409–1413.

    Google Scholar 

  31. Vellenga, E., Rambaldi, A., Ernst, T. J., Ostapovicz, D., and Griffin, J. D. (1988) Independent regulation of M-CSF and G-CSF gene expression in human monocytes. Blood 71, 1529–1532.

    CAS  PubMed  Google Scholar 

  32. Bot, F. J., v. Eijk, L., Schipper, P., and Lowenberg, B. (1989) Effects of human interleukin-3 on granulocytic colony-forming cells in human bone marrow. Blood 73, 1157–1160.

    CAS  PubMed  Google Scholar 

  33. Leary, A. G., Yang, Y.-C., Clark, S. C., Gasson, J. C., Golde, D. W., and Ogawa, M. (1987) Recombinant gibbon interleukin-3 supports formation of human multilineage colonies and blast cell colonies in culture: Comparison with recombinant human granulocyte-macrophage colony stimulating factor. Blood 70, 1343–1348.

    CAS  PubMed  Google Scholar 

  34. Valent, P. Schmidt, G., Besemer, J., Mayer, P., Zenke, G., Liehl, E., Hinterberger, W., Lechner, K., Maurer, D., and Bettelheim, P. (1989) Interleukin-3 is a differentiation factor for human basophils. Blood 73 1763–1769.

    Google Scholar 

  35. Carding, S. R., Jenkinson, E. J., Kingston, R., Hayday, A. C., Bottomly, K., and Owen, J. J. T. (1989) Developmental control of lymphokine gene expression in fetal thymocytes during T cell ontogeny. Proc. Natl. Acad. Sci. USA 86, 3342–3345.

    Article  CAS  PubMed  Google Scholar 

  36. Yang-Snyder, J. A. and Rothenberg, E. V. (1993) Developmental and anatomical patterns of IL-2 gene expression in vivo in the murine thymus. Dev. Immunol. 3, 85–102.

    Article  CAS  PubMed  Google Scholar 

  37. Zúniga-Pflücker, J. C., Smith, K. A., Tentori, L., Pardoll, D. M., Longo, D. L., and Kruisbeek, A. M. (1990) Are the IL-2 receptors expressed in the murine fetal thymus functional? Dev. Immunol. 1, 59–66.

    Article  PubMed  Google Scholar 

  38. Deman, J., Martin, M.-T., Delvenne, P., Humblet, C., Boniver, J., and Defresne, M. P. (1992) Analysis by in situ hybridization of cells expressing mRNA for tumor-necrosis factor in the developing thymus of mice. Dev. Immunol. 2, 103–109.

    Article  CAS  PubMed  Google Scholar 

  39. Wiles, M. V., Ruiz, P., and Imhof, B. A. (1992) Interleukin-7 expression during mouse thymus development. Eur. J. Immunol. 22, 1037–1042.

    Google Scholar 

  40. Lynch, F. and Shevach, E. M. (1992) Activation requirements of newborn thymic gamma delta T cells. J. Immunol. 149, 2307–2314.

    CAS  PubMed  Google Scholar 

  41. Ransom, J., Fischer, M., Mosmann, T., Yokota, T., DeLuca, D., Schumacher, J., and Zlotnik, A. (1987) Interferon-gamma is produced by activated immature mouse thymocytes and inhibits the interleukin 4-induced proliferation of immature thymocytes. J. Immunol 139, 4102–4108.

    CAS  PubMed  Google Scholar 

  42. Zlotnik, A. and Kelner, G. S. (1994) Cytokines in the adult thymus, in Intrathymic T-Cell Development (Nikolic-Zugic, J., R.G. Landes, Austin, TX, p. 64–75.

    Google Scholar 

  43. Zlotnik, A., Ransom, J., Frank, G, Fischer, M., and Howard, M. (1987) Interleukin 4 is a growth factor for activated thymocytes: possible role in T-cell ontogeny. Proc. Natl. Acad. Sci. USA 84, 3856–3860.

    Article  CAS  PubMed  Google Scholar 

  44. Godfrey, D. I., Zlotnik, A., and Suda, T. (1992) Phenotypic and functional characterization of c-kit expression during intrathymic T cell development. J. Immunol. 149, 2281–2285.

    CAS  PubMed  Google Scholar 

  45. Galy, A. H. and Spits, H. (1991) IL-1, IL-4, and IFN-gamma differentially regulate cytokine production and cell surface molecule expression in cultured human thymic epithelial cells. J. Immunol. 147, 3823–3830.

    CAS  PubMed  Google Scholar 

  46. Gimble, J. M., Pietrangeli, C., Henley, A., Dorheim, M. A., Silver, J., Namen, A., Takeichi, M., Goridis, C., and Kincade, P. W. (1989) Characterization of murine bone marrow and spleen-derived stromal cells: analysis of leukocyte marker and growth factor mRNA transcript levels. Blood 74, 303–311.

    Google Scholar 

  47. Harigaya, K., Cronkite, E. P., Miller, M. E., and Shadduck, R. K. (1981) Murine bone marrow cell line producing colony-stimulating factor. Proc. Natl. Acad. Sci. USA 78, 6963–6966.

    Article  CAS  PubMed  Google Scholar 

  48. Hunt, P. Robertson, D., Weiss, D., Rennick, D., Lee, F., and Witte, O. N. (1987) A single bone marrow-derived stromal cell type supports the in vitro growth of early lymphoid and myeloid cells. Cell 48 997–1007.

    Google Scholar 

  49. Akashi, M., Loussararian, A. H., Adelman, D. C., Saito, M., and Koeffler, H. P. (1990) Role of lymphotoxin in expression of interleukin 6 in human fibroblasts. Stimulation and regulation. J. Clin Invest. 85, 121–129.

    Google Scholar 

  50. Fibbe, W. E., Van Damme, J., Billiau, A., Duinkerken, N., Lurvink, E., Ralph, P., Altrock, B. W., Kaushansky, K., Willemze, R., and Falkenburg, J. H. (1988) Human fibroblasts produce granulocyte-CSF, macrophage-CSF, and granulocyte-macrophage-CSF following stimulation by interleukin-1 and poly(rI).poly(rC). Blood 72, 860–866.

    CAS  PubMed  Google Scholar 

  51. Fibbe, W. E., van Damme, J., Billiau, A., Goselink, H. M., Voogt, P. J., van Eeden, G., Ralph, P., Altrock, B. W., and Falkenburg, J. H. (1988) Interleukin 1 induces human marrow stromal cells in long-term culture to produce granulocyte colony-stimulating factor and macrophage colony-stimulating factor. Blood 71, 430–435.

    CAS  PubMed  Google Scholar 

  52. Nemunaitis, J., Andrews, D. F., Crittenden, C., Kaushansky, K., and Singer, J. W. (1989) Response of simian virus 40 (SV40)-transformed, cultured human marrow stromal cells to hematopoietic growth factors. J. Clin. Invest. 83, 593–601.

    Article  CAS  PubMed  Google Scholar 

  53. Slack, J. L., Nemunaitis, J., Andrews, D. F., and Singer, J. W. (1990) Regulation of cytokine and growth factor gene expression in human bone marrow stromal cells transformed with simian virus 40. Blood 75, 2319–2327.

    CAS  PubMed  Google Scholar 

  54. Kaushansky, K., Lin, N., and Adamson, J. W. (1988) Interleukin 1 stimulates fibroblasts to synthesize granulocyte-macrophage and granulocyte colony-stimulating factors: mechanism for the hematopoietic response to inflammation. J. Clin. Invest. 81, 92–97.

    Article  CAS  PubMed  Google Scholar 

  55. Yamato, K., El-Hajjaoui, Z., Kuo, J. F., and Koeffler, H. P. (1989) Granulocyte-macrophage colony-stimulating factor: signals for its mRNA accumulation. Blood 74, 1314–1320.

    CAS  PubMed  Google Scholar 

  56. Bot, F., van Eijk, L., Broeders, L., Aarden, L., and Lowenberg, B. (1989) Interleukin-6 synergizes with M-CSF in the formation of macrophage colonies from purified human marrow progenitor cells. Blood 73, 435–437.

    CAS  PubMed  Google Scholar 

  57. Caracciolo, D. Clark, S. C., and Rovera, G. (1989) Human interleukin-6 supports granulocytic differentiation of hematopoietic progenitor cells and acts synergistically with GM-CSF. Blood 73 666–670.

    Google Scholar 

  58. Zsebo, K. M., Yuschenkoff, V. N., Schiffer, S., Chang, D., McCall, E., Dinarello, C. A., Brown, M. A., Altrock, B., and Bagby, G. C. (1988) Vascular endothelial cells and granulopoiesis: interleukin-1 stimulates release of G-CSF and GM-CSF. Blood 71, 99–103.

    CAS  PubMed  Google Scholar 

  59. Herrmann, F, Oster, W., Meuer, S. C., Lindemann, A., and Mertelsmann, R. H. (1988) Interleukin 1 stimulates T lymphocytes to produce granulocyte-monocyte colony-stimulating factor. J Clin. Invest. 81, 1415–1418.

    Article  CAS  PubMed  Google Scholar 

  60. Allen, T. D., Dexter, T. M., and Simmons, P. J. (1990) Marrow biology and stem cells, in Colony Stimulating Factors: Molecular and Cellular Biology, (Dexter, T. M., Garland, J. M., and Testa, N. G., eds.), Marcel Dekker, New York, pp. 1–38.

    Google Scholar 

  61. Grabstein, K. H., Waldschmidt, T. J., Finkelman, F. D., Hess, B. W., Alpert, A. R., Boiani, N. E., Namen, A. E., and Morrissey, P. J. (1993) Inhibition of murine B and T lymphopoiesis in vivo by an anti-interleukin 7 monoclonal antibody. J. Exp. Med. 178, 257–264.

    Google Scholar 

  62. Namen, A. E., Lupton, S., Hjerrild, K., Wignall, J., Mochizuki, D. Y., Schmeirer, A., Mosley, B., March, C. J., Urdal, D., and Gillis, S. (1988) Stimulation of B cell progenitors by cloned murine interleukin-7. Nature 333, 571.

    Google Scholar 

  63. Peschon, J. J., Morrissey, P. J., Grabstein, K. H., Ramsdell, F. J., Maraskovsky, E., Gliniak, B. C., Park, L. S., Ziegler, S. F., Williams, D. E., Ware, C. B., Meyer, J. D., and Davison, B. L. (1994) Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice. J. Exp. Med. 180, 1955–1960.

    Google Scholar 

  64. von Freeden-Jeffry, U., Vieira, P., Lucian, L. A., McNeil, T., Burdach, S E, and Murray, R. (1995) Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine. J. Exp. Med. 181, 1519–1526.

    Google Scholar 

  65. Rolink, A., Streb, M., Nishikawa, S.-I., and Melchers, F. (1991) The c-kit encoded tyrosine kinase regulates the proliferation of early pre-B cells. Eur. J. Immunol. 21, 2609–2613.

    Article  CAS  PubMed  Google Scholar 

  66. Landreth, K. S., Narayanan, R., and Dorshkind, K. (1992) Insulin-like growth factor-1 regulates B cell differentiation. Blood 80, 1207–1210.

    CAS  PubMed  Google Scholar 

  67. Le, P. T., Tuck, D. T., Dinarello, C. A., Haynes, B. F., and Singer, K. H. (1987) Human thymic epithelial cells produce interleukin 1. J. Immunol. 138, 2520–2526.

    CAS  PubMed  Google Scholar 

  68. Murray, R., Suda, T., Wrighton, N., Lee, F., and Zlotnik, A. (1989) IL-7 is a growth and maintenance factor for mature and immature thymocyte subsets. Int. Immunol. 1, 526–531.

    Article  CAS  PubMed  Google Scholar 

  69. Galy, A. H., Spits, H., and Hamilton, J. A. (1993) Regulation of M-CSF production by cultured human thymic epithelial cells. Lymphokine Cytokine Res. 12, 265–270.

    CAS  PubMed  Google Scholar 

  70. Le, P. T., Lazorick, S., Whichard, L. P., Yang, Y. C., Clark, S. C., Haynes, B. F., and Singer, K. H. (1990) Human thymic epithelial cells produce IL-6, granulocyte-monocyte-CSF, and leukemia inhibitory factor. J. Immunol. 145, 3310–3315.

    Google Scholar 

  71. DeLuca, D. and Mizel, S. B. (1986) I-A-positive nonlymphoid cells and T cell development in murine fetal thymus organ cultures: interleukin 1 circumvents the block in T cell differentiation induced by monoclonal anti-I-A antibodies. J. Immunol. 137, 1435–1441.

    CAS  PubMed  Google Scholar 

  72. Nakano, N., Kikutani, H., and Kishimoto, T. (1990) Differential effects of IL-2 and IL-6 on the development of three distinct precursor T-cell populations in the thymus. Dev. Immunol. 1, 77–84.

    Article  CAS  PubMed  Google Scholar 

  73. Peault, B., Khazaal, I., and Weissman, I. L. (1994) In vitro development of B cells and macrophages from early mouse fetal thymocytes. Eur. J. Immunol. 24, 781–784.

    Article  CAS  PubMed  Google Scholar 

  74. Samaridis, J., Casorati, G., Traunecker, A., Iglesias, A., Gutierrez, J. C., Muller, U., and Palacios, R. (1991) Development of lymphocytes in interleukin 7-transgenic mice. Eur. J. Immunol. 21, 453–460.

    Article  CAS  PubMed  Google Scholar 

  75. Carding, S. R., and Tannishtha. (1994) Cytokines in the fetal thymus, in Intrathymic T-Cell Development, ( Nikolic Zugic, J., ed.), R. G. Landes Company, Austin, TX, p. 46–63.

    Google Scholar 

  76. Haynes, B. F. (1990) Human thymic epithelium and T cell development: current issues and future directions. Thymus 16, 143–157.

    CAS  PubMed  Google Scholar 

  77. Broxmeyer, H. E., Williams, D. E., Lu, L., Cooper, S., Anderson, S. L., Beyer, G. S., Hoffman, R., and Rubin, B. Y. (1986) The suppressive influences of human tumor necrosis factors on bonemarrow hematopoietic progenitor cells from normal donors and patients with leukemia: synergism of tumor necrosis factor and interferon-gamma. J. Immunol. 136, 4487–4495.

    CAS  PubMed  Google Scholar 

  78. Rigby, W. F. C., Ball, E. D., Guyre, P. M., and Fanger, M. W. (1985) The effects of recombinant DNA-derived interferons on the growth of myeloid progenitor cells. Blood 65, 858–861.

    CAS  PubMed  Google Scholar 

  79. Zoumbos, N. C., Djeu, J. Y., and Young, N. S. (1984) Interferon is the suppressor of hematopoiesis generated by stimulated lymphocytes in vitro. J. Immunol. 133, 769–774.

    CAS  PubMed  Google Scholar 

  80. Jacobsen, S. E., Ruscetti, F. W., Dubois, C. M., and Keller, J. R. (1992) Tumor necrosis factor alpha directly and indirectly regulates hematopoietic progenitor cell proliferation: role of colony-stimulating factor receptor modulation. J. Exp. Med. 175, 1759–1772.

    Article  CAS  PubMed  Google Scholar 

  81. Murphy, M., Perussia, B., and Trinchieri, G. (1988) Effects of recombinant tumor necrosis factor, lymphotoxin, and immune interferon on proliferation and differentiation of enriched hematopoietic precursor cells. Exp. Hematol. 16, 131–138.

    CAS  PubMed  Google Scholar 

  82. Peetre, C., Gullberg, U., Nilsson, E., and Olsson, I. (1986) Effects of recombinant tumor necrosis factor on proliferation and differentiation of leukemic and normal hemopoietic cells in vitro: Relationship to cell surface receptor. J. Clin. Invest. 78, 1694–1700.

    Article  CAS  PubMed  Google Scholar 

  83. Roodman, G. D., Bird, A., Hutzler, D., and Montgomery, W. (1987) Tumor necrosis factor-alpha and hematopoietic progenitors: Effects of tumor necrosis factor on the growth of erythroid progenitors CFU-E and BFU-E and the hematopoietic cell lines K562, HL60 and HEL cells. Exp. Hematol. 15, 928–935.

    CAS  PubMed  Google Scholar 

  84. Broxmeyer, H. E., Sherry, B., Lu, L., Cooper, S., Carow, C., Wolpe, S. D., and Cerami, A. (1989) Myelopoietic enhancing effects of murine macrophage inflammatory proteins 1 and 2 on colony formation in vitro by murine and human bone marrow granulocyte/macrophage progenitor cells. J. Exp. Med. 170, 1583–1594.

    Article  CAS  PubMed  Google Scholar 

  85. Broxmeyer, H. E., Sherry, B., Lu, L., Cooper, S., Oh, K.-O., Tekamp-Olson, P., Kwon, B. S., and Cerami, A. (1990) Enhancing and suppressing effects of recombinant murine macrophage inflammatory proteins on colony formation in vitro by bone marrow myeloid progenitor cells. Blood 76, 1110–1116.

    CAS  PubMed  Google Scholar 

  86. Graham, G. J., Wright, E. G., Hewick, R., Wolpe, S.D., Wilkie, N. M., Donaldson, D., Lorimore, S., and Pragnell, I. B. (1990) Identification and characterization of an inhibitor of haemopoietic stem cell proliferation. Nature 344, 442–444.

    Article  CAS  PubMed  Google Scholar 

  87. Maze, R., Sherry, B., Kwon, B. S., Cerami, A., and Broxmeyer, H. E. (1992) Myelosuppressive effects in vivo of purified recombinant murine macrophage inflammatory protein-1 alpha. J. Immunol. 149, 1004–1009.

    CAS  PubMed  Google Scholar 

  88. Eaves, C. J., Cashman, J. D., Kay, R. J., Dougherty, G. J., Otsuka, T., Gaboury, L. A., Hogge, D. E., Lansdorp, P. M., Eaves, A. C., and Humphries, R. K. (1991) Mechanisms that regulate the cell cycle status of very primitive hematopoietic cells in long-term human marrow cultures. II. Analysis of positive and negative regulators produced by stromal cells within the adherent layer. Blood 78, 110–117.

    Google Scholar 

  89. Hatzfeld, J., Li, M. L., Brown, E. L., Sookdeo, H., Levesque, J.P., O’Toole, T., Gurney, C., Clark, S. C., and Hatzfeld, A. (1991) Release of early human hematopoietic progenitors from quiescence by antisense transforming growth factor beta 1 or Rb oligonucleotides. J. Exp. Med 174, 925–929.

    Article  CAS  PubMed  Google Scholar 

  90. Morgan, D. A., Ruscetti, F. W., and Gallo, R. (1976) Selective in vitro growth of T lymphocytes from normal human bone marrows. Science 193, 1007–1008.

    Article  CAS  PubMed  Google Scholar 

  91. Taniguchi, T., Matsui, H., Fujita, T., Takaoka, C., Kashima, N., Yoshimoto, R., and J. Hamuro. (1983) Structure and expression of a cloned cDNA for human interleukin-2. Nature 302, 305–310.

    Google Scholar 

  92. Carding, S. R., Hayday, A. C., and Bottomly, K. (1991) Cytokines in T cell development. Immunol. Today 12, 239–245.

    Article  CAS  PubMed  Google Scholar 

  93. Chen, J., Ma, A., Young, F., and Alt, F. (1994) IL2 receptor alpha chain expression during early B lymphocyte differentiation. Int. Immunol. 6, 1265–1268.

    Article  CAS  PubMed  Google Scholar 

  94. Rolink, A., Grawunder, U., Winkler, T. H., Karasuyama, H., and Melchers, F. (1994) IL-2 receptor a chain (CD25, TAC) expression defines a crucial stage in pre-B cell development. Int. Immunol. 6, 1257–1264.

    Article  CAS  PubMed  Google Scholar 

  95. Reya, T., Bassiri, H., Biancaniello, R., and Carding, S. R. (1998) Thymic stromal cell abnormalities and dysregulated T cell development in IL2-deficient mice. Dev. Immunol. in press.

    Google Scholar 

  96. Nakamura, M., Asao, H., Takeshita, T., and Sugamura, K. (1993) Interleukin-2 receptor heterotrimer complex and intracellular signaling. Sem. Immunol. 17, 309–317.

    Article  Google Scholar 

  97. Grabstein, K. H., Eisenman, J., Shanebeck, K., Rauch, C., Srinivasan, S., Fung, V., Beers, C., Richardson, J., Schoenborn, M. A., Ahdieh, M., Johnson, L., Alderson, M. R., Watson, J. D., Anderson, D. M., and Giri, J. G. (1994) Cloning of a T cell growth factor that interacts with the 13 chain of the interleukin-2 receptor. Science 264, 965–968.

    Article  CAS  PubMed  Google Scholar 

  98. Kondo, M., Ohashi, Y., Tada, K., Nakamura, M., and Sugamura, K. (1994) Expression of the mouse interleukin-2 receptor y chain in various populations of the thymus and spleen. Eur. J. Immunol. 24, 2026–2030.

    Article  CAS  PubMed  Google Scholar 

  99. Russell, S. M., Keegan, A. D., Harada, N., Nakamura, Y., Noguchi, M., Leland, P., Friedmann, M. C., Miyajima, A., Puri, R. K., Paul, W. E., and Leonard, W. J. (1993) Interleukin-2 receptor y chain: A functional component of the interleukin-4 receptor. Science 262, 1880–1883.

    Article  CAS  PubMed  Google Scholar 

  100. Kondo, M., Takeshita, T., Higuchi, M., Nakamura, M., Sudo, T., Nishikawa, S., and Sugamura, K. (1994) Functional participation of the IL-2 receptor gamma chain in IL-7 receptor complexes. Science 263, 1453–1454.

    Article  CAS  PubMed  Google Scholar 

  101. Noguchi, M., Nakamura, Y., Russell, S. M., Ziegler, S. F., Tsang, M., Cao, X., and Leonard, W. J. (1993) Interleukin-2 receptor y chain: a functional component of the interleukin-7 receptor. Science 262, 1877–1880.

    Article  CAS  PubMed  Google Scholar 

  102. Russell, S. M., Johnston, J. A., Noguchi, M., Kawamura, M., Bacon, C. M., Friedmann, M., Berg, M., McVicar, D. W., Witthuhn, B. A., Silvennoinen, O., Goldman, A. S., Schmalstieg, F. C., Ihle, J. N., O’Shea, J. J., and Leonard, W. J. (1994) Interaction of IL-2Rß and yc chains with Jak1 and Jak3: implications for XSCID and XCID. Science 266, 1042–1045.

    Article  CAS  PubMed  Google Scholar 

  103. Giri, J. G., Ahdieh, M., Eisenman, J., Shanebeck, K., Grabstein, K., Kumaki, S., Namen, A., Park, L. S., Cosman, D., and Anderson, D. (1994) Utilization of the ß and y chains of the IL-2 receptor by the novel cytokine IL-15. EMBO J. 13, 2822–2830.

    CAS  PubMed  Google Scholar 

  104. Siegel, J. P., Sharon, M., Smith, P. L., and Leonard, W. L. (1987) The IL-2 receptor ß chain (p70): role in mediating signals for LAK, NK, and proliferative activities. Science 238, 75–78.

    Article  CAS  PubMed  Google Scholar 

  105. Tsudo, M., Goldman, C. K., Bongiovanni, K. F., Chan, W. C., Winton, E. F., Yagita, M., Grimm, E. A., and Waldmann, T. A. (1987) The p75 peptide is the receptor for interleukin 2 expressed on large granular lymphocytes and is responsible for interleukin 2 activation of these cells. Proc. Natl. Acad. Sci. USA 84, 5394–5398.

    Article  CAS  PubMed  Google Scholar 

  106. Arima, N., Kamio, M., Imada, K., Hori, T., Hattori, T., Tsudo, M., Okuma, M., and Uchiyama, T. (1992) Pseudo-high affinity interleukin 2 (IL-2) receptor lacks the third component that is essential for functional IL-2 binding and signaling. J. Exp. Med. 176, 1265–1272.

    Article  CAS  PubMed  Google Scholar 

  107. Asao, H. Takeshita, T., Ishii, N., Kumaki, S., Nakamura, M., and Sugamura, K. (1993) Reconstitution of functional interleukin 2 receptor complexes on fibroblastoid cells: involvement of the cytoplasmic domain of the gamma chain in two distinct signaling pathways. Proc. Natl. Acad. Sci. USA 90 4127–4131.

    Google Scholar 

  108. Taniguchi, T. and Minami, Y. (1993) The IL-2/LL-2 receptor system: a current overview. Cell 73, 5–8.

    Article  CAS  PubMed  Google Scholar 

  109. Voss, S. D., Leary, T. P., Sondel, P. M., and Robb, R. J. (1993) Identification of a direct interaction between interleukin 2 and the p64 interleukin 2 receptor gamma chain. Proc. Natl. Acad. Sci. USA 90, 2428–2432.

    Google Scholar 

  110. Zurawski, S. M., Imler, J.-L., and Zurawski, G. (1990) Partial agonist/antagonist mouse interleukin-2 proteins indicate that a third component of the receptor complex functions in signal transduction. EMBO J. 9, 3899–3905

    CAS  PubMed  Google Scholar 

  111. Imler, J.-L. and Zurawski, G. (1992) Receptor binding and internaliation of mouse interleukin2 derivatives that are partial agonists. J. Biol. Chem. 267, 13,185–13, 190.

    Google Scholar 

  112. Takeshita, T., Asao, H., Ohtani, K., Ishii, N., Kumaki, S., Tanaka, N., Munakata, H., Nakamura, M., and Sugamura, K. (1992) Cloning of the y chain of the human IL-2 receptor. Science 257, 379–382.

    Article  CAS  PubMed  Google Scholar 

  113. Nakamura, Y., Russell, S. M., Mess, S. A., Friedmann, M., Erdos, M., Francois, C., Jacques, Y., Adelstein, S., and Leonard, W. J. (1994) Heterodimerization of the IL2 receptor 3- and y-chain cytoplasmic domains is required for signalling. Nature 369, 330–333.

    Article  CAS  PubMed  Google Scholar 

  114. Nelson, B. H. Lord, J. D., and Greenberg, P. D. (1994) Cytoplasmic domains of the of interleukin 2 receptor 3 and y chains mediate the signal for T-cell proliferation. Nature 369 333–336.

    Google Scholar 

  115. Plaisance, S., Rubenstein, E., Alileche, A., Benoit, P., Jasmin, C, and Azzarone, B. (1993) The IL2 receptor present on human embryonic fibroblasts is functional in the absence of P64/IL2Ry chain. Int. Immunol. 5, 843–848.

    Article  CAS  PubMed  Google Scholar 

  116. Hatakeyama, M., Kono, T., Kobayashi, N., Kawahara, A., Levin, S. D., Perlmutter, R. M., and Taniguchi, T. (1991) Interaction of the IL-2 receptor with the src-family kinase p56“: identification of novel intermolecular association. Science 252, 1523–1528.

    Google Scholar 

  117. Greene, W. C. and Leonard, W. J. (1986) The human interleukin-2 receptor. Ann. Rev. Immunol. 4, 69–95.

    Article  CAS  Google Scholar 

  118. De la Hera, A., Toribio, M. L., Marquez, C., Marcos, M. A., Cabrero, E., and Martinez-A, C. (1986) Differentiation of human mature thymocytes: existence of a T3+4–8- intermediate stage. Eur. J. Immunol. 16, 653–658.

    Article  PubMed  Google Scholar 

  119. Raulet, D. H. (1985) Expression and function of interleukin-2 receptors on immature thymocytes. Nature 314, 101–103.

    Article  CAS  PubMed  Google Scholar 

  120. Toribio, M. L., De la Hera, A., Marcos, M. A., Marquez, C., and Martinez-A, C. (1989) Activation of the interleukin 2 pathway precedes CD3-T cell receptor expression in thymic development. Differential growth requirements of early and mature intrathymic subpopulations. Eur. J. Immunol. 19, 9–15.

    Article  CAS  PubMed  Google Scholar 

  121. Tanaka, T., Takeuchi, Y., Shiohara, T., Kitamura, F., Nagasaka, Y., Hamamura, K., Yagita, H., and Miyasaka, M. (1992) In utero treatment with monoclonal antibody to IL-2 receptor 3-chain completely abrogates development of Thy-1+ dendritic epidermal cells. Int. Immunol. 4, 487–491.

    Article  CAS  PubMed  Google Scholar 

  122. Skinner, M., Le Gros, G., Marbrook, J., and Watson, J. D. (1987) Development of fetal thymocytes in organ cultures: Effect of interleukin 2. J. Exp. Med. 165, 1481–1493.

    Article  CAS  PubMed  Google Scholar 

  123. Waanders, G. A. and Boyd, R. L. (1990) The effects of interleukin 2 on early and late thymocyte differentiation in foetal thymus organ culture. Int. Immunol. 2, 461–468.

    Article  CAS  PubMed  Google Scholar 

  124. Waanders, G. A., Godfrey, D. I., and Boyd, R. L. (1989) Modulation of T-cell differentiation in murine fetal thymus organ cultures. Thymus 13, 73–82.

    CAS  PubMed  Google Scholar 

  125. Habu, S., Okumura, K., Diamantstein, T., and Shevach, E. (1985) Expression of interleukin 2 receptor on murine fetal thymocytes. Eur. J. Immunol. 15, 456–460.

    Article  CAS  PubMed  Google Scholar 

  126. von Boehmer, H., Crisanti, A., Kisielow, P., and Haas, W. (1985) Absence of growth by most receptor-expressing fetal thymocytes in the presence of interleukin-2. Nature 314, 539–540.

    Article  Google Scholar 

  127. Jenkinson, E. J., Kingston, R., and Owen, J. J. T. (1987) Importance of IL-2 receptors in intra-thymic generation of cells expressing T-cell receptors. Nature 329, 160–162.

    Article  CAS  PubMed  Google Scholar 

  128. Plum, J., and de Smedt, M. (1988) Differentiation of thymocytes in fetal organ culture: lack of evidence for the functional role of the interleukin 2 receptor expressed by prothymocytes. Eur. J. Immunol. 18, 795–799.

    Article  CAS  PubMed  Google Scholar 

  129. Tentori, L., Longo, D. L., Zúniga-Pflücker, J. C., Wing, C., and Kruisbeek, A. M. (1988) Essential role of the interleukin 2- interleukin 2 receptor pathway in thymocyte maturation in vivo. J. Exp. Med. 168, 1741–1747.

    Article  CAS  PubMed  Google Scholar 

  130. Zúniga-Pflücker, J. C. and Kruisbeek, A. M. (1990) Intrathymic radioresistant stem cells follow an IL-2/IL-2R pathway during thymic regeneration after sublethal irradiation. J. Immunol. 144, 3736–3740.

    PubMed  Google Scholar 

  131. Gutierrez-Ramos, J. C., Martinez, A. C., and Kohler, G. (1990) Analysis ofT cell subpopulation in human IL-2R-alpha transgenic mice: expansion of Thy.1.2- thymocytes and depletion of double-positive T cell precursors. Immunol. Res. 140, 661–674.

    Google Scholar 

  132. Nishi, M., Ishida, Y., and Honjo, T. (1988) Expression of functional interleukin-2 receptors in human light chain/Tac transgenic mice. Nature 331, 267–269.

    Article  CAS  PubMed  Google Scholar 

  133. Schorle, H., Holtschke, T., Hunig, T., Schimpl, A., and Horak, I. (1991) Development and function of T cells in mice rendered interleukin-2 deficient by gene targeting. Nature 352, 621–624.

    Article  CAS  PubMed  Google Scholar 

  134. Horak, I., Löhler, J., Ma, A., and Smith, K. A. (1995) Interleukin-2 deficient mice: a new model to study autoimmunity and self-tolerance. Immunol. Rev. 148, 35–43.

    Article  CAS  PubMed  Google Scholar 

  135. Sadlack, B., Merz, H., Schorle, H., Schimpl, A., Feller, A. C., and Horak, I. (1993) Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene. Cell 75, 253–261.

    Article  CAS  PubMed  Google Scholar 

  136. Krämer, S., Schimpl, A., and Hunig, T. (1995) Immunopathology of interleukin (IL) 2-deficient mice: thymus dependence and supression by thymus-depedent cells with and intact IL-2 gene. J. Exp. Med. 182, 1769–1776.

    Article  PubMed  Google Scholar 

  137. Hanke, T., Mitnacht, R., Boyd, R., and Hünig, T. (1994) Induction of interleukin-2 receptor 13-chain expression by self-recognition in the thymus. J. Exp. Med. 180, 1629–1636.

    Article  CAS  PubMed  Google Scholar 

  138. Lúdvíksson, B. R., Gray, B., Strober, W., and Ehrhardt, R. O. (1997) Dysregulated intrathymic development in the IL2-deficient mouse leads to colitis-inducing thymocytes. J. Immunol. 158, 104–111.

    PubMed  Google Scholar 

  139. Rocha, B., Lehuen, A., and Papiernik, M. (1988) IL2-dependent proliferation of thymic accessory cells. J Immunol. 140, 1076–1080.

    CAS  PubMed  Google Scholar 

  140. Contractor, N. V., Bassiri, H., Reya, T., Park, A. Y., Baumgart, D. C., Wasik, M., Emerson, S. G., and Carding, S. R. (1998) Lymphoid hyperplasia, autoimmunity and compromised intestinal intraepithelial lymphocyte development in colitis-free gnotobiotic Interleukin 2-deficient mice. J. Immunol. 160, 385–394.

    Google Scholar 

  141. Murphy, K., Heimberger, A., and Loh, D. (1990) Induction by antigen of intrathymic apoptosis of CD4+CD8+TCRlo thymocytes in vivo. Science 250, 1720–1723.

    Article  CAS  PubMed  Google Scholar 

  142. Kneitz, B., Herrmann, T., Yonehara, S., and Schimpl, A. (1995) Normal clonal expansion but impaired Fas-mediated cell death and anergy induction in interleukin-2-deficient mice. Eur. J. Immunol. 25, 2572–2577.

    Article  CAS  PubMed  Google Scholar 

  143. Sadlack, B., Löhler, J., Schorle, H., Klebb, G., Haber, H., Sickel, E., Noelle, R. J., and Horak, I. (1995) Generalized autoimmune disease in interleukin-2-deficient mice is triggered by an uncontrolled activation and proliferation of CD4+ T cells. Eur. J. Immunol. 25, 3053–3059.

    Article  CAS  PubMed  Google Scholar 

  144. Willerford, D. M., Chen, J., Ferry, J. A., Davidson, L., Ma, A., and Alt, F. W. (1995) Interleukin2 receptor a chain regulates the size and content of the peripheral lymphoid compartment. Immunity 3, 521–530.

    Article  CAS  PubMed  Google Scholar 

  145. Suzuki, H., Kundig, T. M., Furlonger, C., Wakeman, A., Timms, E., Matsuyama, T., Schmits, R., Simard, J. J. L., Ohashi, P., Griesser, H., Taniguchi, T., Paige, C. J., and Mak, T. W. (1995) Deregulated T cell activation and autoimmunity in mice lacking interleukin-2 receptor ß. Science 268, 1472–1476.

    Google Scholar 

  146. Krämer, S., Mamalaki, C., Horak, I., Schimpl, A., Kioussis, D., and Hünig, T. (1994) Thymic selection and peptide-induced activation of T cell receptor-transgenic CD8 T cells in interleukin2-deficient mice. Eur. J. Immunol. 24, 2317–2322.

    Article  Google Scholar 

  147. Turner, M., Mee, P. J., Costello, P. S., Williams, O., Price, A. A., Duddy, L. P., Furlong, M. T., Geahlen, R. L., and Tybulewicz, V. L. (1995) Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk. Nature 378, 298–302.

    Article  CAS  PubMed  Google Scholar 

  148. Cao, X., Shores, E. W., Hu-Li, J., Anver, M. R., Kelsall, B. L., Russell, S. M., Drago, J., Noguchi, M., Grinberg, A., Bloom, E. T., Paul, W. E., Katz, S. I., Love, P. E., and Leonard, W. J. (1995) Defective lymphoid development in mice lacking expression of the common cytokine receptor y chain. Immunity 2, 223–238.

    Article  CAS  PubMed  Google Scholar 

  149. DiSanto, J. P., Müller, W., D. Guy-Grand, Fischer, A., and Rajewsky, K. (1995) Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor y chain. Proc. Natl. Acad. Sci. USA 92, 377–381.

    Article  CAS  PubMed  Google Scholar 

  150. Suzuki, H., Duncan, G., Takimoto, H., and Mak, T. W. (1997) Abnormal development of intestinal intraepithelial lymphocytes and peripheral natural killer cells in mice lacking the IL2receptor (3 chain. J. Exp. Med. 185, 499–505.

    Article  CAS  PubMed  Google Scholar 

  151. Jung, L. K. L., Hara, T., and Fu, S. M. (1984) Detection and functional studies of p60–65 (Tac antigen) on activated human B cells. J. Exp. Med. 160, 1597–1565.

    Article  CAS  PubMed  Google Scholar 

  152. Longo, D., L., Gelman, E., P., Cossman, J., Young, R., A., Gallo, R. C., O’Brien, S., and Matis, L. A. (1984) Isolation of HTLV-transformed B-lymphocyte clone from a patient with HTLVassociated adult T cell leukemia. Nature 310, 505–506.

    Article  CAS  PubMed  Google Scholar 

  153. Muraguchi, A., Kehri, J. H., Longo, D. L., Volkman, D. J., Smith, K. A., and Fauci, A. S. (1985) Interleukin 2 receptors on human B cells: implications for the role of interleukin 2 in human B cell function. J. Exp. Med. 161, 181–197.

    Article  CAS  PubMed  Google Scholar 

  154. Robb, R. J. (1984) Interleukin-2: The molecule and its function. Immunology Today 5, 203–206.

    Article  CAS  Google Scholar 

  155. Jianzhu, C., Ma, A., Young, F., and Alt, F. (1994) IL-2 receptor a chain expression during early B lymphocyte differentiation. Int. Immunol. 6, 1265–1268.

    Article  Google Scholar 

  156. Reya, T., Yang-Snyder, J. A., Rothenberg, E. V., and Carding, S. R. (1996) Regulated expression and function of CD122 (Interleukin-2/Interleukin-15R-13) during lymphoid development. Blood 87, 190–201.

    CAS  PubMed  Google Scholar 

  157. Horton, J. and Ratcliffe, N. (1996) Evolution of immunity, in Immunology, (Roitt, I., Brostoff, J., and Male, D., eds.), Mosby, London, p. 15. 1–15. 22.

    Google Scholar 

  158. Gambacorti-Passerini, C., Hank, J. A., Borchert, A., Moore, K., Malkovska, V., and Sondel, P. (1991) In vivo effects of multiple cycles of recombinant interleukin-2 (IL2) on peripheral granulocyte-macrophage hematopoietic progenitors circulating in the blood of cancer patients. Tumori 77, 420–422.

    CAS  PubMed  Google Scholar 

  159. Schaafsma, M. R., Fibbe, W. E., Van Der Harst, D., Duinkerken, N., Brand, A., Osanto, S., Franks, C. R., Willemze, R., and Falkenberg, J. H. F. (1990) Increased numbers of circulating haematopoietic progenitor cells after treatment with high-dose interleukin-2 in cancer patients. Brit. J. Haematol. 76, 180–185.

    Article  CAS  Google Scholar 

  160. Tritarelli, E., Rocca, E., Testa, U., Boccoli, G., Camagna, A., Calabresi, F., and Peschle, C. (1991) Adoptive immunotherapy with high-dose interleukin-2 kinetics of circulating progenitors correlates with interleukin-6, granulocyte colony stimulating factor level. Blood 77, 741–749.

    CAS  PubMed  Google Scholar 

  161. Michalevicz, R., Campana, D., Katz, F. E., Janossy, G., and Hoffbrand, A. V. (1988) Recombinant interleukin 2 and anti-Tac influence the growth of enriched multipotent hemopoietic progenitors: proposed hypothesis for different responses in early and late progenitors. Leukemia Res. 12, 113–121.

    Google Scholar 

  162. Baccarini, M., Schwinger, M., and Lohmann-Matthes, M.-L. (1989) Effect of human recombinant IL2 on murine macrophage precursors. J. Immunol 142, 118–125.

    CAS  PubMed  Google Scholar 

  163. Reya, T., Contractor, N. V., Couzens, M. C., Wasik, M. A., Emerson, S. G., and Carding, S. R. (1998) Abnormal myelocytic cell development in interleukin-2 (IL2) deficient mice: evidence for the involvement of IL2 in myelopoiesis. Blood 91, 1–14.

    Google Scholar 

  164. Pericle, F., Liu, J. H., Diaz, J. I., Blanchard, D. K., Wei, S., Forni, G., and Djeu, J. Y. (1994) Interleukin-2 prevention of apoptosis in human neutrophils. Eur. J. Immunol. 24, 440–444.

    Google Scholar 

  165. Weinberg, K. P. R. (1990) Severe combined immunodeficiency due to a specific defect in the production of interleukin-2. N. Engl. J. Med. 322, 1718–1723.

    Article  CAS  PubMed  Google Scholar 

  166. Ye, J. Ortaldo, J. R., Conlon, K., R. Winkler-Pickett, and Young, H. A. (1995) Cellular and molecular mechanisms of IFN-gamma production induced by IL-2 and IL-12 in a human NK cell line. J. Leuk. Biol. 58 225–233.

    Google Scholar 

  167. Estrov, Z., Roifman, C., Wang, Y. P., Grunberger, T., Gelfand, E. W., and Freedman, M. H. (1986) The regulatory role of interleukin 2-responsive T lymphocytes on early and mature erythroid progenitor proliferation. Blood 67, 1607–1610.

    Google Scholar 

  168. Skettino, S., Phillips, J., Camer, L., Nagler, A., and Greenberg, P. (1988) Selective generation of erythroid burst-promoting activity by recombinant human interleukin 2-stimulated human T lymphocytes. Blood 71, 907–914.

    CAS  PubMed  Google Scholar 

  169. Quinones, R. R. (1993) Hematopoietic engraftment and graft failure after bone marrow transplantation. Am. J. Pediat. Hematol-Oncol. 15, 3–17.

    Article  CAS  Google Scholar 

  170. Garland, J. M. and Dexter, T. M. (1982) Expression of 20-alpha hydroxysteroid dehydrogenase in murine long-term bone marrow cultures. Eur. J. Immunol. 12, 998–1001.

    Article  CAS  PubMed  Google Scholar 

  171. Burdach, S. and Levitt, L. (1987) Receptor-specific inhibition of bone marrow erythropoiesis by reconbinant DNA-derived interleukin-2. Blood 69, 1368–1375.

    CAS  PubMed  Google Scholar 

  172. Frassoni, F., Bacigalupo, A., Podesta, M., van Lint, M. T., Piaggio, G., and Marmont, A. (1982) Generation of CFU-C suppressor T cells in vitro. III. Failure ofmitogen-primed T cells from patients with chronic granulocytic leukemia to inhibit the growth of normal CFU-C. Blood 60, 1447–1452.

    CAS  PubMed  Google Scholar 

  173. Kerndrup, G. and Hokland, P. (1988) Natural killer cell-mediated inhibition of bone marrow colony formation (CFU-GM) in refractory anaemia (preleukaemia): evidence for patient-specific cell populations. Br. J. Haematol. 69, 457–462.

    Article  CAS  PubMed  Google Scholar 

  174. Bacigalupo, A., Podesta, M., Mingari, M., Moretta, L., Van Lint, M., and Marmont, A. (1980) Immune suppression of hematopoiesis in aplastic anemia: activity of T-gamma lymphocytes. J. Immunol. 125, 1449–1453.

    CAS  PubMed  Google Scholar 

  175. Zoumbos, N. C., Gascon, P., Djeu, J. Y., and Young, N. S. (1985) Interferon is a mediator of hematopoietic suppression in aplastic anemia in vitro and possibly in vivo. Proc. Nall. Acad. Sci. USA 82, 188–192.

    Article  CAS  Google Scholar 

  176. Rennick, D., Yang, G., Muller-Sieburg, C., Smith, C., Arai, N., Takabe, Y., and 1. Gemmel, L. (1987) Interleukin 4 (B-cell stimulatory factor 1) can enhance or antagonize the factor-dependent growth of hemopoietic progenitor cells. Proc. Natl. Acad. Sci. USA 84, 6889–6893.

    Article  CAS  PubMed  Google Scholar 

  177. Wang, J., Lin, Q., Langston, H., and Cooper, M. (1995) Resident bone marrow macrophages produce Type 1 interferons that can selectively inhibit interleukin-7-driven growth of B lineage cells. Immunity 3, 475–484.

    Article  CAS  PubMed  Google Scholar 

  178. Selleri, C., Sato, T., Anderson, S., Young, N. S., and Maciejewski, J. P. (1995) Interferon-gamma and tumor necrosis factor-alpha suppress both early and late stages of hematopoiesis and induce programmed cell death. J. Cell. Physiol. 165, 538–546.

    Google Scholar 

  179. Maciejewski, J. P., Weichold, F. F., and Young, N. S. (1994) HIV-1 suppression ofhematopoiesis in vitro mediated by envelope glycoprotein and TNF-alpha. J. Immunol. 153, 4303–4310.

    CAS  PubMed  Google Scholar 

  180. Ma, A., Datta, M., Margosian, E., Chen, J., and Horak, I. (1995) T cell, but not B cells are required for bowel inflammation in interleukin-2 deficient mice. J. Exp. Med. 182, 1567–1572.

    Article  CAS  PubMed  Google Scholar 

  181. Westen, H. and Bainton, D. F. (1979) Association of alkaline-phosphatase-positive reticulum cells in bone marrow with granulocytic precursors. J. Exp. Med. 150, 919–937.

    Article  CAS  PubMed  Google Scholar 

  182. Plaisance, S., Rubenstein, E., Alileche, A., Krief, P., Augery-Bourget, Y., Sahraoui, Y., Jasmin, C., Suarez, C., and Azzarone, B. (1992) Expression of interleukin-2 receptor on human fibroblasts and its biological significance. Int. Immunol. 4, 739–746.

    Article  CAS  PubMed  Google Scholar 

  183. Gong, J. K. (1978) Endostial marrow: a rich source of hematopoietic stem cells. Science 199, 1443–1445.

    Article  CAS  PubMed  Google Scholar 

  184. Lord, B. I. and Hendry, H. H. (1972) The distribution of haemopoietic colony-forming units in the mouse femur and its modification by X-rays. Br. J. Radiol. 45, 110–115.

    Article  CAS  PubMed  Google Scholar 

  185. Chan, S. H. and Metcalf, D. (1972) Local production of colony-stimulating factor within the bone marrow: role of nonhematopoietic cells. Blood 40, 646–649.

    CAS  PubMed  Google Scholar 

  186. Feyen, J. H., Elford, P., Di Padova, F. E., and Trechsel, U. (1989) Interleukin-6 is produced by bone and modulated by parathyroid hormone. J. Bone Min. Res. 4, 633–638.

    Google Scholar 

  187. Horowitz, M. C., Coleman, D. L., Flood, P. M., Kupper, T. S., and Jilka, R. L. (1989) Parathyroid hormone and lipopolysaccharide induce murine osteoblast-like cells to secrete a cytokine indistinguishable from granulocyte-macrophage colony-stimulating factor. J. Clin. Invest. 83, 149–157.

    Article  CAS  PubMed  Google Scholar 

  188. Horowitz, M. C., Coleman, D. L., Ryaby, J. T., and Einhorn, T. A. (1989) Osteotropic agents induce the differential secretion of granulocyte-macrophage colony-stimulating factor by the osteoblast cell line MC3T3–E1. J. Bone Min. Res. 4, 911–921.

    Article  CAS  Google Scholar 

  189. Lowik, C. W., van der Pluijm, G., Bloys, H., Hoekman, K., Bijvoet, O. L., Aarden, L. A., and Papapoulos, S. E. (1989) Parathyroid hormone (PTH) and PTH-like protein (PLP) stimulate interleukin-6 production by osteogenic cells: a possible role of interleukin-6 in osteoclasto-genesis. Biochem. Biophys. Res. Comm. 162, 1546–1552.

    Google Scholar 

  190. Benayahu, D., Horowitz, M., Zipori, D., and Wientroub, S. (1992) Hemopoietic functions of marrow-derived osteogenic cells. Calcified Tissue Int. 51, 195–201.

    Article  CAS  Google Scholar 

  191. Taichman, R. S. and Emerson, S. G. (1994) Human osteoblasts support hematopoiesis through the production of granulocyte colony-stimulating factor. J. Exp. Med. 179, 1677–1682.

    Article  CAS  PubMed  Google Scholar 

  192. Taichman, R. S., Reilly, M. J., and Emerson, S. G. (1996) Human osteoblasts support human hematopoietic progenitor cells in in vitro bone marrow cultures. Blood 87, 518–524.

    CAS  PubMed  Google Scholar 

  193. Friedenstein, A. J., Chailakhjan, R. K., and Lalykina, K. S. (1970) The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet. 3, 393–403.

    CAS  PubMed  Google Scholar 

  194. Friedenstein, A. J., Deriglasova, U. F., Kulagina, N. N., Panasuk, A. F., Rudakowa, S. F., Luria, E. A., and Ruadkow, I. A. (1974) Precursors for fibroblasts in different populations of hematopoietic cells as detected by the in vitro colony assay method. Exp. Hematol. 2, 83–92.

    CAS  PubMed  Google Scholar 

  195. Friedenstein, A. J. (1976) Precursor cells of mechanocytes. Int. Rev. Cytol. 47, 327–359.

    Article  CAS  PubMed  Google Scholar 

  196. Hagenaars, C. E., van der Kraan, A. A., Kawliarang-de Hass, E. W., Visser, J. W., and Nijweide, P. J. (1989) Osteoclast formation from cloned pluripotent hemopoietic stem cells. Bone Miner. 6, 179–189.

    Article  CAS  PubMed  Google Scholar 

  197. Scheven, B. A. A., Visser, J. W. M., and Nijweide, P. J. (1986) In vitro osteoclast generation from different bone marrow fractions, including a highly enriched haemapoietic stem cell population. Nature 321, 79–81.

    Article  CAS  PubMed  Google Scholar 

  198. Jee, W. S. S. and Nolan, P. D. (1963) Origin of osteoclasts from fusion of phagocytes. Nature 200, 225–226.

    Article  CAS  PubMed  Google Scholar 

  199. Ikuta, K., Kina, T., MacNeil, I., Uchida, N., Peault, B., Chien, Y. H., and Weissman, I. L. (1990) A developmental switch in thymic lymphocyte maturation potential occurs at the level of hematopoietic stem cells. Cell 62, 863–874.

    Article  CAS  PubMed  Google Scholar 

  200. Ikuta, K., Uchida, N., Friedman, J., and Weissman, I. L. (1992) Lymphocyte development from stem cells. Ann. Rev. Immunol. 10, 759–783.

    Article  CAS  Google Scholar 

  201. Hardy, R. R. and Hayakawa, K. (1991) A developmental switch in B lymphopoiesis. Proc. Natl. Acad. Sci. USA 88, 11,550–11, 554.

    Google Scholar 

  202. Naito, M. (1993) Macrophage heterogeniety in development and differentiation. Arch. Histol. Cytol. 56, 331–351.

    Article  CAS  PubMed  Google Scholar 

  203. Naito, M., Umeda, S., Yamamoto, T., Moriyama, H., Umezu, H., Hasegawa, G., Usuda, H., Shultz, L. D. and Takahashi, K. (1996) Development, differentiation and phenotypic heterogeniety of murine tissue macrophages. J. Leuk. Biol. 59, 133–138.

    CAS  Google Scholar 

  204. Stamatoyannopoulos, G. andNienhuis, A. W. (1987) Human hemoglobin switching, inMolecular Basis of Blood Disease (Stamatoyannopoulos, G., ed.), Saunders, Philadelphia, p. 66–84.

    Google Scholar 

  205. Hayakawa, K., Tarlinton, D., and Hardy, R. R. (1994) Absence of MHC class II expression distinguishes fetal from adult B lymphopoiesis in mice. J. Immunol. 152, 4801–4807.

    CAS  PubMed  Google Scholar 

  206. Lam, K.-P., and Stall, A. M. (1994) Major histocompatibility complex class II expression distinguishes two distinct B cell developmental pathways during ontogeny. J. Exp. Med. 180, 507–516.

    Article  CAS  PubMed  Google Scholar 

  207. Lansdorp, P. M., Dragowska, W., and Mayani, H. (1993) Ontogeny-related changes in proliferative potential of human hematopoietic cells. J. Exp. Med. 178, 787–791.

    Article  CAS  PubMed  Google Scholar 

  208. Moore, M. A. S. and Metcalf, D. (1970) Ontogeny of the haemopoietic system: Yolk sac origin of in vivo and in vitro colony forming cells in the developing mouse embryo. Br. J. Haematol. 18, 279–296.

    Article  CAS  PubMed  Google Scholar 

  209. Christensen, R. D. (1988) Developmental changes in pluripotent hematopoietic progenitors. Early Hum. Del). 16, 195–205.

    Article  CAS  Google Scholar 

  210. Stein, P. L., Vogel, H., and Soriano, P. (1994) Combined deficiencies of Src, Fyn, and Yes tyrosine kinases in mutant mice. Genes Del). 8, 1999–2007.

    Article  CAS  Google Scholar 

  211. Kondo, M., Takeshita, T., Naoto, I., Nakamura, M., Watanabe, S., Arai, K.-I., and Sugamura, K. (1993) Sharing of the interleukin-2 (IL-2) receptor y chain between receptors for IL-2 and IL-4. Science 262, 1874–1876.

    Google Scholar 

  212. Bachmann, M. F., Schorle, H., Kuhn, R., Muller, W., Hengartner, H., Zinkernagel, R. M., and Horak, I. (1995) Antiviral immune responses in mice deficient for both interleukin-2 and interleukin-4. J. Virol. 69, 4842–4846.

    CAS  PubMed  Google Scholar 

  213. Sadlack, B., Kuhn, R., Schorle, H., Rajewsky, K., Muller, W., and Horak, I. (1994) Development and proliferation of lymphocytes in mice deficient for both interleukins-2 and -4. Eur. J. Immunol. 24, 281–284.

    Article  CAS  PubMed  Google Scholar 

  214. Minasi, L.-A., Kamogawa, Y., Carding, S. R., Bottomly, K., and Flavell, R. A. (1993) Ablation of interleukin-2—producing cells isolated from transgenic mice. J. Exp. Med. 177, 2205–2210.

    Article  Google Scholar 

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Reya, T., Carding, S.R. (1998). The Role of Cytokines in Hematolymphoid Development. In: Monroe, J.G., Rothenberg, E.V. (eds) Molecular Biology of B-Cell and T-Cell Development. Contemporary Immunology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4757-2778-4_9

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  • DOI: https://doi.org/10.1007/978-1-4757-2778-4_9

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