Lymphoid Development and Function in IL-7R-Deficient Mice

  • Jacques J. Peschon
  • Brian C. Gliniak
  • Philip Morrissey
  • Eugene Maraskovsky
Part of the Contemporary Immunology book series (CONTIM)


The stages of B- and T-cell progenitor development have been thoroughly defined on the basis of cell surface marker expression, antigen receptor gene rearrangement, and cytokine responsiveness. For example, interleukin-7 (IL-7) was originally identified as a factor produced by bone marrow stromal cells that could support the proliferation of B-cell precursors (1,2). The IL-7 responsive B-lineage cells were clearly defined in vitro using sorted B-cell precursor populations and shown to express B220, CD43 heat stable antigen (HSA), and to carry heavy-chain gene rearrangements (3). IL-7 responsiveness is lost following light-chain gene rearrangement and acquisition of the pre-B-cell phenotype (4). IL-7 is also a potent mitogen for thymocytes (5). In a similar fashion, it has been established that the CD44+CD25 fraction of CD4CD8 thymocytes, comprising <1% of the total thymocyte population, is IL-7 responsive, whereas the predominant CD4+CD8+ thymocyte subpopulation is not (6).


Severe Combine Immunodeficiency Disease Thymocyte Development Cell Surface Marker Expression Lymphoid Development Cytokine Responsiveness 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Namen, A. E., Lupton, S., Hjerrild, K., Wignall, J., Mochizuki, D. Y., Schmierer, A., Mosley, B., March, C. J., Urdal, D., Gillis, S., Cosman, D., and Goodwin, R. G. (1988) Stimulation of B-cell progenitors by cloned murine interleukin-7. Nature 333, 571–573.PubMedCrossRefGoogle Scholar
  2. 2.
    Namen, A. E., Schmierer, A. E., March, C. J., Overell, R. W., Park, L. S., Urdal, D. L., and Mochizuki, D. Y. (1988) B cell precursor growth-promoting activity. Purification and characterization of a growth factor active on lymphocyte precursors. J. Exp. Med. 167, 988–1002.PubMedCrossRefGoogle Scholar
  3. 3.
    Hardy, R. R., Carmack, C. E., Shinton, S. A., Kemp, J. D., and Hayakawa, K. (1991) Resolution and characterization of pro-B and pre-pro-B cell stages in normal mouse bone marrow. J. Exp. Med. 173, 1213–1225.PubMedCrossRefGoogle Scholar
  4. 4.
    Henderson, A. J., Narayanan, R., Collins, L., and Dorshkind, K. (1992) Status of xL chain gene rearrangements and c-kit and IL-7 receptor expression in stromal cell-dependent pre-B cells. J. Immunol. 149, 1973–1979.PubMedGoogle Scholar
  5. 5.
    Conlon, P. J., Morrissey, P. J., Nordan, R. P., Grabstein, K. H., Prickett, K. S., Reed, S. G., Goodwin, R., Cosman, D., and Namen, A. E. (1989) Murine thymocytes proliferate in direct response to interleukin-7. Blood 74, 1368–1373.PubMedGoogle Scholar
  6. 6.
    Plum, J., De Smedt, M., and Leclercq, G. (1993) Exogenous IL-7 promotes the growth of CD3–CD4–CD8–CD44+CD25+i-precursor cells and blocks the differentiation pathway of TCR-a13 cells in fetal thymus organ culture. J. Immunol. 150, 2706–2716.PubMedGoogle Scholar
  7. 7.
    Bhatia, S. K., Tygrett, L. T., Grabstein, K. H., and Waldschmidt, T. J. (1995) The effect of in vivo IL-7 deprivation on T cell maturation. J. Exp. Med. 181, 1399–1409.PubMedCrossRefGoogle Scholar
  8. 8.
    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.PubMedCrossRefGoogle Scholar
  9. 9.
    Sudo, T., Nishikawa, S., Ohno, N., Akiyama, N., Tamakoshi, M., Yoshida, H., and Nishikawa, S.-I. (1993) Expression and function of the interleukin 7 receptor in murine lymphocytes. Proc. Natl. Acad. Sci. USA 90, 9125–9129.PubMedCrossRefGoogle Scholar
  10. 10.
    von Freeden-Jeffry, U., Vieira, P., Lucian, L. A., McNeil, T., Burdach, S. E. G., 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.CrossRefGoogle Scholar
  11. 11.
    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
  12. 12.
    DiSanto, J. P., Müller, W., Guy-Grand, D., 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.PubMedCrossRefGoogle Scholar
  13. 13.
    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.PubMedCrossRefGoogle Scholar
  14. 14.
    Armitage, R. J., Ziegler, S. F., Friend, D. J., Park, L. S., and Fanslow, W. C. (1992) Identification of a novel low-affinity receptor for human interleukin7. Blood 79, 1738–1745.Google Scholar
  15. 15.
    Park, L. S., Friend, D. J., Schmierer, A. E., Dower, S. K., and Namen, A. E. (1990) Murine interleukin 7 (IL-7) receptor. Characterization on an IL-7dependent cell line. J. Exp. Med. 171, 1073–1089.PubMedCrossRefGoogle Scholar
  16. 16.
    Whitlock, C. A., Robertson, D., and Witte, O. N. (1984) Murine B cell lymphopoiesis in long term culture. J. Immunol. Methods 67, 353–369.PubMedCrossRefGoogle Scholar
  17. 17.
    Sawada, M., Itoh, Y., Suzumura, A., and Marunouchi, T. (1993) Expression of cytokine receptors in cultured neuronal and glial cells. Neurosci. Lett. 160, 131–134.PubMedCrossRefGoogle Scholar
  18. 18.
    Mehler, M. F., Rozental, R., Dougherty, M., Spray, D. C., and Kessler, J. A. (1993) Cytokine regulation of neuronal differentiation of hippocampal progenitor cells. Nature 362, 62–65.PubMedCrossRefGoogle Scholar
  19. 19.
    Hozumi, K., Kondo, M., Nozaki, H., Kobori, A., Nishimura, T., Nishikawa, S.-I., Sugamura, K., and Habu, S. (1994) Implication of the common y chain of the IL-7 receptor in intrathymic development of pro-T cells. Int. Immunol. 6, 1451–1454.PubMedCrossRefGoogle Scholar
  20. 20.
    Zúniga-Pflücker, J. C., Di, J., and Lenardo, M. J. (1995) Requirement for TNF-a and IL-la in fetal thymocyte commitment and differentiation. Science 268, 1906–1909.PubMedCrossRefGoogle Scholar
  21. 21.
    Godfrey, D. I. and Zlotnik, A. (1993) Control points in early T-cell development. Immunol. Today 14, 547–553.PubMedCrossRefGoogle Scholar
  22. 22.
    Rothenberg, E. V. (1992) The development of functionally responsive T cells. Adv. Immunol. 51, 85–214.PubMedCrossRefGoogle Scholar
  23. 23.
    Spangrude, G. J. and Scollay, R. (1990) Differentiation of hematopoietic stem cells in irradiated mouse thymic lobes. Kinetics and phenotype of progeny. J. Immunol. 145, 3661–3668.PubMedGoogle Scholar
  24. 24.
    Muegge, K., Vila, M. P., and Durum, S. K. (1993) Interleukin-7: a cofactor for V(D)J rearrangement of the T cell receptor 13 gene. Science 261, 93–95.PubMedCrossRefGoogle Scholar
  25. 25.
    Groettrup, M. and von Boehmer, H. (1993) A role for a pre-T-cell receptor in T-cell development. Immunol. Today 14, 610–614.PubMedCrossRefGoogle Scholar
  26. 26.
    Morrissey, P. J., Goodwin, R. G., Nordan, R. P., Anderson, D., Grabstein, K. H., Cosman, D., Sims, J., Lupton, S., Acres, B., Reed, S. G., Mochizuki, D., Eisenman, J., Conlon, P. J., and Namen, A. E. (1989) Recombinant interleukin-7, pre-B cell growth factor, has costimulatory activity on purified mature T cells. J. Exp. Med. 169, 707–716.PubMedCrossRefGoogle Scholar
  27. 27.
    Maraskovsky, E., Teepe, M., Morrissey, P. J., Miller, R. E., Lynch, D. H., Braddy, S., and Peschon, J. J. (1996) Impaired Survival and Proliferation in IL-7 Receptor-Deficiency Peripheral T Cells. J. Immunol. 157, 5315–5323.PubMedGoogle Scholar
  28. 28.
    Lynch, D. H. and Miller, R. E. (1994) Interleukin 7 promotes long-term in vitro growth of antitumor cytotoxic T lymphocytes with immunotherapeutic efficacy in vivo. J. Exp. Med. 179, 31–42.PubMedCrossRefGoogle Scholar
  29. 29.
    Zeng, Y. X., Takahashi, H., Shibata, M., and Hirokawa, K. (1994) JAK3 Janus kinase is involved in interleukin 7 signal pathway. FEBS Lett. 353, 289–293.PubMedCrossRefGoogle Scholar
  30. 30.
    Thomis, D. C., Gurniak, C. B., Tivol, E., Sharpe, A. H., and Berg, L. J. (1995) Defects in B lymphocyte maturation and T lymphocyte activation in mice lacking Jak3. Science 270, 794–797.PubMedCrossRefGoogle Scholar
  31. 31.
    Nosaka, T., van Deursen, J. M. A., Tripp, R. A., Thierfelder, W. E., Witthuhn, B. A., McMickle, A. P., Doherty, P. C., Grosveld, G. C., and Ihle, J. N. (1995) Defective lymphoid development in mice lacking Jak3. Science 270, 800–802.PubMedCrossRefGoogle Scholar
  32. 32.
    Ziegler, S. F., Tough, T. W., Franklin, T. L., Armitage, R. J., and Alderson, M. R. (1991) Induction of macrophage inflammatory protein-113 gene expression in human monocytes by lipopolysaccharide and IL-7. J. Immunol. 147, 2234–2239.PubMedGoogle Scholar
  33. 33.
    Alderson, M. R., Tough, T. W., Ziegler, S. F., and Grabstein, K. H. (1991) Interleukin 7 induces cytokine secretion and tumoricidal activity by human peripheral blood monocytes. J. Exp. Med. 173, 923–930.PubMedCrossRefGoogle Scholar
  34. 34.
    Gessner, A., Vieth, M., Will, A., Schröppel, K., and Röllinghoff, M. (1993) Interleukin-7 enhances antimicrobial activity against Leishmania major in murine macrophages. Infect. Immun. 61, 4008–4012.PubMedGoogle Scholar
  35. 35.
    Kondo, M., Takeshita, T., Higuchi, M., Nakamura, M., Sudo, T., Nishikawa, S.-I., and Sugamura, K. (1994) Functional participation of the IL-2 receptor y chain in IL-7 receptor complexes. Science 263, 1453–1454.PubMedCrossRefGoogle Scholar
  36. 36.
    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.PubMedCrossRefGoogle Scholar
  37. 37.
    Noguchi, M., Yi, H., Rosenblatt, H. M., Filipovich, A. H., Adelstein, S., Modi, W. S., McBride, O. W., and Leonard, W. J. (1993) Interleukin-2 receptor y chain mutation results in X-linked severe combined immunodeficiency in humans. Cell 73, 147–157.PubMedCrossRefGoogle Scholar
  38. 38.
    Friend, S. L., Hosier, S., Nelson, A., Foxworthe, D., Williams, D. E., and Farr, A. (1994) A thymic stromal cell line supports in vitro development of surface IgM+ B cells and produces a novel growth factor affecting B and T lineage cells. Exp. Hematol. 22, 321–328.PubMedGoogle Scholar
  39. 39.
    Gougeon, M.-L., Drean, G., Le Deist, F., Dousseau, M., Fevrier, M., Diu, A., Theze, J., Griscelli, C., and Fischer, A. (1990) Human severe combined immunodeficiency disease. Phenotypic and functional characteristics of peripheral B lymphocytes. J. Immunol. 145, 2873–2879.PubMedGoogle Scholar
  40. 40.
    Conley, M. E. (1991) X-linked severe combined immunodeficiency. Clin. Immunol. Immunopathol. 61, S94–99.PubMedCrossRefGoogle Scholar
  41. 41.
    Winkler, T. H., Melchers, F., and Rolink, A. G. (1995) Interleukin-3 and interleukin-7 are alternative growth factors for the same B-cell precursors in the mouse. Blood 85, 2045–2051.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Jacques J. Peschon
  • Brian C. Gliniak
  • Philip Morrissey
  • Eugene Maraskovsky

There are no affiliations available

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