TCR-Independent Development of Pluripotent T-Cell Precursors

  • Wu Li
  • Ferenc Livak
  • Howard T. Petrie
Part of the Contemporary Immunology book series (CONTIM)


The various contributions to this book are intended to serve as a collection of opinions based on contemporary knowledge. The opinion the authors will seek to illustrate here, that T-cell differentiation is not driven by T-cell receptor (TCR) expression, is an unconventional view and in reality, will probably need to be tempered by nuance and circumstance. Nonetheless, most of the data that have lead to the conventional view (i.e., T-cell development that is directed by TCR expression) could be reinterpreted to support the proposal that TCR expression, although absolutely required for T-cell survival and function, does not drive differentiation, but rather, facilitates survival. It is noteworthy to point out that many of the early stages of intrathymic differentiation occur prior to any TCR gene recombination, illustrating the concept that differentiation can occur without a TCR. Further, what immunologists refer to as “selection” is, in fact, a common function among developing tissues: survival, mediated by the absolute requirement for a given gene product at some specific point during development. Given the absence of a required gene product, as can happen in the mutation of any gene, the affected cell dies. Nevertheless, other developmental events occur independently of such a defect, up to and including the point where its essential function is required. In the case of the TCR, the frequency of such “mutations” is abnormally high, because of the random nature of the recombination and recognition processes. As will be discussed, it is nevertheless conceivable and useful, to view T-cell development as occurring independently of TCR expression, with TCR+ cells surviving the developmental process, whereas TCR cells die. Likewise, an attempt will be made to make the similar point that TCR-α/β versus γ/δ expression on a given cell does not induce T lineage divergence; rather, it facilitates the survival of those cells that express the appropriate TCR isotype. Finally, it is important to state that the concepts presented here are directed toward an understanding of T-cell development in the adult murine thymus. Fetal T-cell development, although similar to that of the adult, differs in many important ways (1,2), and extrapolation between these models may not be accurate.


Gene Rearrangement Lineage Commitment Thymocyte Development Immature Thymocyte Allelic Exclusion 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Shortman, K. and Wu, L. (1996) Early T lymphocyte progenitors. Ann. Rev. Immunol. 14, 29–47.CrossRefGoogle Scholar
  2. 2.
    Boyd, R. L., Tucek, C. L., Godfrey, D. I., Izon, D. J., Wilson, T. J., Davidson, N. J., Bean, A. G. D., Ladyman, H. M., Ritter, M. A., and Hugo, P. (1993) Inside the thymus. Immunol. Today 14, 445–459.PubMedCrossRefGoogle Scholar
  3. 3.
    Petrie, H. T., Strasser, A., Harris, A. W., Hugo, P., and Shortman, K. (1993) CD4+8- and CD4–8+ mature thymocytes require different post-selection processing for final development. J. Immunol. 151, 1273–1279.Google Scholar
  4. 4.
    Fowlkes, B. J., Edison, L., Mathieson, B. J., and Chused, T. M. (1985) Early T lymphocytes: differentiation in vivo of adult intrathymic precursor cells. J. Exp. Med. 162, 802–822.Google Scholar
  5. 5.
    Lesley, J., Trotter, J., Schulte, R., and Hyman, R. (1990) Phenotypic analysis of the early events during repopulation of the thymus by the bone marrow prothymocyte. Cell. Immunol. 128, 63–78.Google Scholar
  6. 6.
    Pearse, M., Wu, L., Egerton, M., Wilson, A., Shortman, K., and Scollay, R. (1989) An early thymocyte development sequence marked by transient expression of the IL-2 receptor. Proc. Natl. Acad. Sci. USA 86, 1614–1618.PubMedCrossRefGoogle Scholar
  7. 7.
    Shimonkevitz, R. P., Husmann, L. A., Bevan, M. J., and Crispe, I. N. (1987) Transient expression of IL-2 receptor precedes the differentiation of immature thymocytes. Nature 329, 157–159.PubMedCrossRefGoogle Scholar
  8. 8.
    Wilson, A., D’Amico, A., Ewing, T., Scollay, R., and Shortman, K. (1988) Subpopulations of early thymocytes: a cross-correlation flow cytometric analysis of adult mouse Ly-2-L3T4(CD8–CD4-) thymocytes using eight different surface markers. J. Immunol. 140, 1461–1469.PubMedGoogle Scholar
  9. 9.
    Shortman, K., Egerton, M., Spangrude, G. J., and Scollay, R. (1990) The generation and fate of thymocytes. Sem. Immunol. 2, 3–12.Google Scholar
  10. 10.
    Godfrey, D. I., Kennedy, J., Mombaerts, P., Tonegawa, S., and Zlotnik, A. (1994) Onset of TCR-ß gene rearrangement and role of TCR-ß expression during CD3–CD4-CD8- thymocyte differentiation. J. Immunol. 152, 4783–4792.PubMedGoogle Scholar
  11. 11.
    Petrie, H. T., Pearse, M., Scollay, R., and Shortman, K. (1990) Development of immature thymocytes: initiation of CD3, CD4 and CD8 acquisition parallels down-regulation of the interleukin-2 receptor a-chain. Eur. J. Immunol. 20, 2813–2816.PubMedCrossRefGoogle Scholar
  12. 12.
    Petrie, H. T., Livak, F., Burtrum, D., and Mazel, S. (1995) T cell receptor gene recombination patterns and mechanisms: cell death, rescue, and T cell production. J. Exp. Med. 182, 121–127.PubMedCrossRefGoogle Scholar
  13. 13.
    Bruno, L., Rocha, B., Rolink, A., Von Boehmer, H., and Rodewald, H. R. (1995) Intra-and extra-thymic expression of the pre-T cell receptor alpha gene. Eur. J. Immunol. 25, 1877–1982.PubMedCrossRefGoogle Scholar
  14. 14.
    Groettrup, M., Ungewiss, K., Azogui, O., Palacios, R., Owen, M. J., Hayday, A. C., and von Boehmer, H. (1993) A novel disulfide-linked heterodimer on pre-T-cells consists of the T-cell receptor beta chain and a 33 kd glycoprotein. Cell 75, 283–294.PubMedCrossRefGoogle Scholar
  15. 15.
    Saint-Ruf, C., Ungewiss, K., Groettrup, M., Bruno, L., Fehling, H. J., and von Boehmer, H. (1994) Analysis and expression of a cloned pre-T cell receptor gene. Science 266, 1208–1212.PubMedCrossRefGoogle Scholar
  16. 16.
    Nikolic-Zugic, J., Moore, M. W., and Bevan, M. J. (1989) Characterization of the subset of immature thymocytes which can undergo rapid in vitro differentiation. Eur. J. Immunol. 19, 649–653.PubMedCrossRefGoogle Scholar
  17. 17.
    Petrie, H. T., Hugo, P., Scollay, R., and Shortman, K. (1990) Lineage relationships and developmental kinetics of immature thymocytes: CD3, CD4 and CD8 acquisition in vivo and in vitro. J. Exp. Med. 172, 1583–1590.PubMedCrossRefGoogle Scholar
  18. 18.
    Dudley, E. C., Petrie, H. T., Shah, L. M., Owen, M. J., and Hayday, A. C. (1994) T cell receptor beta chain gene rearrangement and selection during thymocyte development in adult mice. Immunity 1, 83–93.PubMedCrossRefGoogle Scholar
  19. 19.
    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
  20. 20.
    Li, C., Wu, L., Antica, M., Shortman, K., and Johnson, G. R. (1995) Purified murine long-term in vivo hemopoietic repopulating cells are not prothymocytes. Exp. Hematol. 23, 21–25.PubMedGoogle Scholar
  21. 21.
    Spangrude, G. J., Heimfeld, S., and Weissman, I. L. (1988) Purification and characterization of mouse hematopoietic stem cells. Science 241, 58–62.PubMedCrossRefGoogle Scholar
  22. 22.
    Antica, M., Wu, L., Shortman, K., and Scollay, R. (1994) Thymic stem cells in the mouse bone marrow. Blood 84, 111–117.PubMedGoogle Scholar
  23. 23.
    Wu, L., Li, C. L., and Shortman, K. (1996) Thymic dendritic cell precursors: relationship to the T-lymphocyte lineage and phenotype of the dendritic cell progeny. J. Exp. Med. 184, 903–911.PubMedCrossRefGoogle Scholar
  24. 24.
    Pénit, C., Lucas, B., and Vasseur, F. (1995) Cell expansion and growth arrest phases during the transition from precursor CD4−8− to immature CD4+8+ thymocytes in normal and genetically modified mice. J. Immunol. 154, 5103–5113.PubMedGoogle Scholar
  25. 25.
    Tourigny, M. R., Mazel, S., Burtrum, D. B., and Petrie, H. T. (1997) T Cell receptor (TCR)-ß gene recombination: dissociation from cell cycle regulation and developmental progression during T cell ontogeny. J. Exp. Med. 185, 1549–1556.Google Scholar
  26. 26.
    Wu, L., Scollay, R., Egerton, M., Pearse, M., Spangrude, G. J., and Shortman, K. (1991) CD4 expressed on earliest T-lineage precursor cells in the adult murine thymus. Nature 349, 71–74.PubMedCrossRefGoogle Scholar
  27. 27.
    Rodewald, H., Kretzschmar, K., Takeda, S., Hohl, C., and Dessing, M. (1994) Identification of pro-thymocytes in murine fetal blood: T lineage commitment can precede thymus colonization. EMBO J. 13, 4229–4240.PubMedGoogle Scholar
  28. 28.
    Wu, L., Antica, M., Johnson, G. R., Scollay, R., and Shortman, K. (1991) Developmental potential of the earliest precursor cells from the adult mouse thymus. J. Exp. Med. 174, 1617–1627.PubMedCrossRefGoogle Scholar
  29. 29.
    Matsuzaki, Y., Gyotoku, J., Ogawa, M., Nishikawa, S., Katsura, Y., Gachelin, G., and Nakauchi, H. (1993) Characterization of c-kit positive intrathymic stem cells that are restricted to lymphoid differentiation. J. Exp. Med. 178, 1283–1291.PubMedCrossRefGoogle Scholar
  30. 30.
    Ardavin, C., Wu, L., Li, C., and Shortman, K. (1993) Thymic dendritic cells and T cells develop simultaneously within the thymus from a common precursor population. Nature 362, 761–763.PubMedCrossRefGoogle Scholar
  31. 31.
    Wu, L., Vremec, D., Ardavin, C., Winkel, K., Suss, G., Georgiou, H., Maraskovsky, E., Cook, W., and Shortman, K. (1995) Mouse thymus dendritic cells: kinetics of development and changes in surface markers during maturation. Eur. J. Immunol. 25, 418–425.PubMedCrossRefGoogle Scholar
  32. 32.
    Zúniga-Pflücker, J. C., Jiang, D., and Lenardo, M. J. (1995) Requirement for TNF-alpha and IL-1 alpha in fetal thymocyte commitment and differentiation. Science 268, 1906–1909.PubMedCrossRefGoogle Scholar
  33. 33.
    Bosma, G. C., Custer, R. P., and Bosma, M. J. (1983) A severe combined immunodeficiency mutation in the mouse. Nature 10, 527–530.CrossRefGoogle Scholar
  34. 34.
    von Boehmer, H. (1990) Developmental biology of T cells in T cell-receptor transgenic mice. Ann. Rev. Immunol. 8, 531–556.CrossRefGoogle Scholar
  35. 35.
    Mombaerts, P. Clarke, A. R., Hooper, M. L., and Tonegawa, S. (1991) Creation of a large genomic deletion at the T-cell antigen receptor 0-subunit locus in mouse embryonic stem cells by gene targeting. Proc. Natl. Acad. Sci. USA 88 3084–3087.Google Scholar
  36. 36.
    Mombaerts, P., Clarke, A. R., Rudnicki, M. A., Iacomini, J., Itohara, S., Lafaille, J. J., Wang, L., Ichikawa, Y., Jaenisch, R., Hooper, M. L., and Tonegawa, S. (1992) Mutations in T-cell antigen receptor genes a and ß block thymocyte development at different stages. Nature 360, 225–231.PubMedCrossRefGoogle Scholar
  37. 37.
    Philpott, K. L., Viney, J. L., Kay, G., Rastan, S., Gardiner, E. M., Chae, S., Hayday, A. C., and Owen, M. J. (1992) Lymphoid development in mice congenitally lacking T-cell receptor-a/ß expressing cells. Science 256, 1448–1452.PubMedCrossRefGoogle Scholar
  38. 38.
    Malissen, M., Trucy, J., Jouvin-Marche, E., Cazenave, P.-A., Scollay, R., and Malissen, B. (1992) Regulation of TCR a and ß gene allelic exclusion during T-cell development. Immunol. Today 13, 315–322.PubMedCrossRefGoogle Scholar
  39. 39.
    Godfrey, D. I. and Zlotnik, A. (1993) Control points in early T-cell development. Immunol. Today 14, 547–553.PubMedCrossRefGoogle Scholar
  40. 40.
    Pardoll, D. M., Fowlkes, B. J., Bluestone, J. A., Kruisbeek, A., Maloy, W. L., Coligan, J. E., and Schwartz, R. H. (1987) Differential expression of two distinct T-cell receptors during thymocyte development. Nature 326, 79–81.PubMedCrossRefGoogle Scholar
  41. 41.
    Dillon, S. R. and Fink, P. J. (1995) Thymic selection events mediated by the pre-TCR do not depend upon a limiting ligand. Int. Immunol. 7, 1363–1373.PubMedCrossRefGoogle Scholar
  42. 42.
    Tonegawa, S. (1983) Somatic generation of antibody diversity. Nature 302, 575–581.PubMedCrossRefGoogle Scholar
  43. 43.
    Schatz, D. G., Oettinger, M. A., and Schlissel, M. S. (1992) VDJ recombination: molecular biology and regulation. Annu. Rev. Immunol. 10, 359–383.CrossRefGoogle Scholar
  44. 44.
    Anderson, S. J. and Perlmutter, R. M. (1996) A signalling pathway governing early thymocyte maturation. Immunol. Today 16, 99–105.CrossRefGoogle Scholar
  45. 45.
    Lin, W. C. and Desiderio, S. (1994) Cell cycle regulation of VDJ recombination-activating protein RAG-2. Proc. Natl. Acad. Sci. USA 91, 2733–2737.PubMedCrossRefGoogle Scholar
  46. 46.
    Hoffman, E. S., Passoni, L., Crompton, T., Leu, T. M. J., Schatz, D. G., Koff, A., Owen, M. J., and Hayday, A. C. (1996) Productive T-cell receptor 0-chain gene rearrangement: coincident regulation of cell cycle and clonality during development in vivo. Genes Dey. 10, 948–962.CrossRefGoogle Scholar
  47. 47.
    Roth, D. B., Nakajima, P. B., Menetski, J. P., Bosma, M. J., and Gellert, M. (1992) VDJ recombination in mouse thymocytes: double-strand breaks near T cell receptor 6 rearrangement signals. Cell 69, 41–53.PubMedCrossRefGoogle Scholar
  48. 48.
    Egerton, M., Shortman, K., and Scollay, R. (1990) The kinetics of immature murine thymocyte development in vivo. Int. Immunol. 24, 1903–1907.Google Scholar
  49. 49.
    Xu, Y., Davidson, L., Alt, F. W., and Baltimore, D. (1996) Function of the pre-T-cell receptor a chain in T-cell development and allelic exclusion at the T-cell receptor 13 locus. Proc. Natl. Acad. Sci. USA 93, 2169–2173.PubMedCrossRefGoogle Scholar
  50. 50.
    Li, Z., Dordai, D. I., Lee, J., and Desiderio, S. (1996) A conserved degradation signal regulates RAG-2 accumulation during cell division and links V(D)J recombination to the cell cycle. Immunity 5, 575–589.PubMedCrossRefGoogle Scholar
  51. 51.
    Norment, A. M., Forbush, K. A., Nguyen, N., Malissen, M., and Perlmutter, R. M. (1997) Replacement of pre-T cell receptor signalling functions by CD4 coreceptor. J. Exp. Med. 185, 121–130.PubMedCrossRefGoogle Scholar
  52. 52.
    Zlotnik A. and Moore, T. A. (1995) Cytokine production and requirements during T-cell development. Corr. Opin. Immunol. 7, 206–213.CrossRefGoogle Scholar
  53. 53.
    Shortman K. and Petrie, H. T. (1990) Interleukins and T-cell development in the thymus. Res. Immunol. 141, 280.CrossRefGoogle Scholar
  54. 54.
    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
  55. 55.
    Akashi, K. M., Von Freeden-Jeffrey, U., Murray, R., and Weissman, I. L. (1997) Bc1–2 rescues T lymphopoiesis in IL-7 receptor deficient mice. Cell 89, 1033–1041.PubMedCrossRefGoogle Scholar
  56. 56.
    Maraskovsky, E., O’Reilly, L. A., Teepe, M., Corcoran, L. M., Peschon, J. J., and Strasser, A. (1997) Bc1–2 can rescue T lymphocyte development in interleukin-7 receptor-deficient mice but not in mutant rag-14- mice. Cell 89, 1011–1019.PubMedCrossRefGoogle Scholar
  57. 57.
    Appasamy, P. M., Kenniston, T. W., Jr., Weng, Y., Holt, E. C., Kost, J., and Chambers, W. H. (1993) Interleukin 7-induced expression of specific T cell receptor-y variable region genes in murine fetal liver cultures. J. Exp. Med. 178, 2201–2206.PubMedCrossRefGoogle Scholar
  58. 58.
    Muegge, K., Vila, M. P., and Dumm, S. K. (1993) Interleukin-7: a cofactor for V(D)J rearrangement of the T cell receptor 13-gene. Science 261, 93–95.Google Scholar
  59. 59.
    Billips, L. G., Nunez, C. A., Bertrand, F. E. I., Stankovic, A. K., Gartland, G. L., Burrows, P. D., and Cooper, M. D. (1995) Immunoglobulin recombinase gene activity is modulated reciprocally by interleukin 7 and CD19 in B cell progenitors. J. Exp. Med. 182, 973–982.Google Scholar
  60. 60.
    Oosterwegel, M. A., Haks, M. C., Jeffry, U., Murray, R., and Kruisbeek, A. M. (1997) Induction of TCR gene rearrangements in uncommitted stem cells by a subset of IL-7 producing, MHC class II-expressing thymic stromal cells. Immunity 6, 351–360.PubMedCrossRefGoogle Scholar
  61. 61.
    Crompton, T., Outram, S. V., Buckland, J., and Owen, M. J. (1997) A transgenic T cell receptor restores thymocyte differentiation in interleukin-7 receptor a chain-deficient mice. Eur. J. Immunol. 27, 100–104.Google Scholar
  62. 62.
    Li, Y., Pezzano, M., Philp, D., Reid, V., and Guyden, J. (1992) Thymic nurse cells exclusively bind and internalize CD4+CD8+ thymocytes. Cell. Immunol. 140, 495–506.PubMedCrossRefGoogle Scholar
  63. 63.
    Peifer, M. (1997) 13-Catenin as oncogene: the smoking gun. Science 275, 1752, 1753.CrossRefGoogle Scholar
  64. 64.
    Müller, K. M., Luedecker, C. J., Udey, M. C., and Farr, A. G. (1997) Involvement of E-cadherin in thymus organogenesis and thymocyte maturation. Immunity 6, 257–264.PubMedCrossRefGoogle Scholar
  65. 65.
    Crompton, T., Gilmour, K. C., and Owen, M. J. (1996) The MAP kinase pathway controls differentiation from double-negative to double-positive thymocyte. Cell 86, 243–251.PubMedCrossRefGoogle Scholar
  66. 66.
    Hughes, P. E., Renshaw, M. W., Pfaff, M., Forsyth, J., Keivens, V. M., Schwartz, M. A., and Ginsberg, M. H. (1997) Suppression of integrin activation: a novel function of a ras/raf-initiated MAP kinase pathway. Cell 88, 521–530.Google Scholar
  67. 67.
    Wadsworth, S. A., Halvorson, M. J., and Coligan, J. E. (1992) Developmentally regulated expression of the 134 integrin on immature mouse thymocytes. J. Immunol. 149, 421–428.PubMedGoogle Scholar
  68. 68.
    Hemmings, B. A. (1997) Akt signaling linking membrane events to life and death decisions. Science 275, 628–630.PubMedCrossRefGoogle Scholar
  69. 69.
    Salomon, D. R., Mojcik, C. F., Chang, A. C., Wadsworth, S., Adams, D. H., Coligan, J. E., and Shevach, E. M. (1994) Constitutive activation of integrin a4/β1 defines a unique stage of human thymocyte development. J. Exp. Med. 179, 1573–1584.PubMedCrossRefGoogle Scholar
  70. 70.
    Wadsworth, S. A., Chang, A. C., Hong, M.-J. P., Halvorson, M. J., Otto, S., and Coligan, J. E. (1995) Expression of a novel integrin 13 chain epitope and anti-131 antibody-mediated enhancement of fibronectin binding are dependent on the stage ofT cell differentiation. J. Immunol. 154, 2125–2133.PubMedGoogle Scholar
  71. 71.
    Asarnow, D. M., Kuziel, W. A., Bonyhadi, M., Tigelaar, R. E., and Tucker, P. W. Allison, J. P. (1988) Limited diversity of y6 antigen receptor genes ofThy-l+dendritic epidermal cells. Ce11 55, 837–847.Google Scholar
  72. 72.
    Elliott, J. F., Rock, E. P., Patten, P. A., Davis, M. M., and Chien, Y. (1988) The adult T-cell receptor 6-chain is diverse and distinct from that of fetal thymocytes. Nature 331, 627–631.PubMedCrossRefGoogle Scholar
  73. 73.
    Itohara, S., Nakanishi, N., Kanagawa, O., Kubo, R., and Tonegawa, S. (1989) Monoclonal antibodies specific to native murine T-cell receptor gamma delta: analysis of gamma delta T cells during thymic ontogeny and in peripheral lymphoid organs. Proc. Natl. Acad. Sci. USA 86, 5094–5098.PubMedCrossRefGoogle Scholar
  74. 74.
    Petrie H. T., Scollay, R., and Shortman, K. (1992) Commitment to the TCR-a/ß or 7/8 lineages can occur just prior to the onset of CD4 and CD8 expression among immature thymocytes. Eur. J. Immunol. 22, 2185.PubMedCrossRefGoogle Scholar
  75. 75.
    Hayday, A. C., Saito, H., Gillies, S. D., Kranz, D. M., Tanagawa, G., Eisen, H. N., and Tonegawa, S. (1985) Structure, organization, and somatic rearrangement of the T cell gamma genes. Cell 40, 259–269.PubMedCrossRefGoogle Scholar
  76. 76.
    Livak, F., Petrie, H. T., Crispe, I. N., and Schatz, D. G. (1995) In-frame TCR d gene rearrangements play a critical role in the aß/y8 T cell lineage decision. Immunity 2, 617–627.PubMedCrossRefGoogle Scholar
  77. 77.
    Nakajima, P. B., Menetski, J. P., Roth, D. B., Gellert, M., and Bosma, M. J. (1995) V-D-J rearrangements at the T cell receptor S locus in mouse thymocytes of the aß lineage. Immunity 3, 609–621.PubMedCrossRefGoogle Scholar
  78. 78.
    Ishida, I., Verbeek, S., Bonneville, M., Itohara, S., and Berns, A. (1990) T-cell receptor 78 and y transgenic mice suggest a role of a y gene silencer in the generation of aß T cells. Proc. Natl. Acad. Sci. USA 87, 3067–3071.PubMedCrossRefGoogle Scholar
  79. 79.
    Wilson, A., Held, W., and Macdonald, H. R. (1994) Two waves ofrecombinase gene expression in developing thymocytes. J. Exp. Med. 179, 1355–1360.PubMedCrossRefGoogle Scholar
  80. 80.
    Wilson, A., de Villartay, J. P., and MacDonald, H. R. (1996) T cell receptor S gene rearrangement and T early a (TEA) expression in immature aß lineage thymocytes: implications for aß/y6 lineage commitment. Immunity 4, 37–45.PubMedCrossRefGoogle Scholar
  81. 81.
    Sim, G., Olsson, C., and Augustin, A. (1995) Commitment and maintenance of the aß and yS T cell lineages. J. Immunol. 154, 5821–5831.PubMedGoogle Scholar
  82. 82.
    Dudley, E. C., Girardi, M., Owen, M. J., and Hayday, A. C. (1995) Alpha-beta and gamma-delta T cells can share a late common precursor. Curr. Biol. 5, 659–669.PubMedCrossRefGoogle Scholar
  83. 83.
    Burtrum, D. B., Kim, S., Dudley, E. C., Hayday, A. C., and Petrie, H. T. (1996) TCR gene recombination and a/ß-7/8 lineage divergence: productive TCR-ß rearrangement is neither exclusive nor preclusive of y/8 cell development. J. Immunol. 157, 4293–4296.PubMedGoogle Scholar
  84. 84.
    Mertsching, E., Wilson, A., MacDonald, H. R., and Ceredig, R. (1997) T cell receptor a gene rearrangement and transcription in adult thymic yS cells. Eur. J. Immunol. 27, 389–396.PubMedCrossRefGoogle Scholar
  85. 85.
    Bonneville, M., Ishida, I., Mombaerts, P., Katsuki, M., Verbeek, S., Berns, A., and Tonegawa, S. (1989) Blockage of aß T-cell development by TCR yS transgenes. Nature 342, 931–934.PubMedCrossRefGoogle Scholar
  86. 86.
    Dent, A. L., Matis, L. A., Hooshmand, F., Widacki, S. M., Bluestone, J. A., and Hedrick, S. M. (1990) Self-reactive yS cells are eliminated in the thymus. Nature 343, 714–719.PubMedCrossRefGoogle Scholar
  87. 87.
    Kersh, G. J., Hooshmand, F. F., and Hedrick, S. M. (1995) Efficient maturation of alpha-beta lineage thymocytes to the CD4+CD8+ stage in the absence ofTCR-ß rearrangement. J. Immunol. 154, 5706–5714.PubMedGoogle Scholar
  88. 88.
    Fenton, R. G., Marrack, P., Kappler, J. W., Kanagawa, O., and Seidman, J. G. (1988) Isotypic exclusion of yS T cell receptors in transgenic mice bearing a rearranged ß-chain gene. Science 241, 1089–1092.PubMedCrossRefGoogle Scholar
  89. 89.
    von Boehmer, H., Bonneville, M., Ishida, I., Ryser, S., Lincoln, G., Smith, R. T., Kishi, H., Scott, B., Kisielow, P., and Tonegawa, S. (1988) Early expression of a T-cell receptor beta-chain transgene suppresses rearrangement of the V gamma 4 gene segment. Proc. Natl. Acad. Sci. USA 85, 9729–9732.Google Scholar
  90. 90.
    Bruno, L., Fehling, H. J., and von Boehmer, H. (1996) The α/ß T cell receptor can replace the γ/δ receptor in the development of γ/ δ lineage cells. Immunity 5, 343–352.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Wu Li
  • Ferenc Livak
  • Howard T. Petrie

There are no affiliations available

Personalised recommendations