Leukemia pp 111-130 | Cite as

Differentiation of T Lymphocytes

  • J. J. T. Owen
Conference paper
Part of the Life Sciences Research Reports book series (DAHLEM, volume 30)

Abstract

Differentiation of T cells from stem cells to mature, functional subsets is discussed. Arguments concerning the level of maturation achieved by pre-T cells and the absolute necessity of intrathymic processing are evaluated. Emphasis is placed on the crucial role of the thymus in T cell differentiation, and recently acquired information about the heterogeneous thymic stromal cell types should provide a sound basis for further work on intrathymic events. The use of phenotypic markers and functional studies to analyze T cell lineage relationships is discussed in the context of some of the conflicting data available.

Keywords

Migration Leukemia Haas Deoxyguanosine Transferase 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. (1).
    Ando, I., and Hurme, M. 1981. Self-MHC-restricted cytotoxic T-cell responses without thymic influence. Nature 289: 494–495.PubMedCrossRefGoogle Scholar
  2. (2).
    Bach, J-F., and Goldstein, G. 1980. Newer concepts of thymic hormones. Thymus 2: 1–4.Google Scholar
  3. (3).
    Barclay, A.N., and Mason, D.W. 1982. Induction of la antigen in rat epidermal cells and gut epithelium by immunological stimuli. J. Exp. Med. 156: 1665–1676.PubMedCrossRefGoogle Scholar
  4. (4).
    Barclay, A.N., and Mayrohofer, G. 1981. Bone marrow origin of la-positive cells in the medulla of the rat thymus. J. Exp. Med. 153: 1660–1671.CrossRefGoogle Scholar
  5. (5).
    Batuman, O.A.; Caro, J.; Schmidt, R.R.; and Hauptman, S.P. 1983. Macromolecular insoluble cold globulin (MICG): a marker for pluripotential hemopoietic stem cells. J. Immunol. 130: 1051–1055.PubMedGoogle Scholar
  6. (6).
    Beller, D.I., and Unanue, E.R. 1980. I-A antigens and antigen-presenting function of thymic macrophages. J. Immunol. 124: 1443–1450.Google Scholar
  7. (7).
    Besedovsky, H.O.; Del Rey, A.; and Sorkin, E. 1979. Role of prethymic cells in acquisition of self-tolerance. J. Exp. Med. 150: 1351–1358.PubMedCrossRefGoogle Scholar
  8. (8).
    Chen, B.P.P., and Splitter, G.A. 1983. Transplantation tolerance: Lyt-l+2- helper T cells require a second proliferative signal to overcome Lyt 1-2+ suppressor T cell activity. J. Immunol. 131: 57–63.PubMedGoogle Scholar
  9. (9).
    Ching, L-M., and Miller, R.S. 1982. Development of cytotoxic T lymphocyte precursor cells in T cell colonies grown in vitro. J. Immunol. 129: 2345–2351.PubMedGoogle Scholar
  10. (10).
    Cordier, A.C., and Heremans, J.F. 1975. Nude mouse embryo. Ectodermal nature of the primordial thymic defect. Scand. J. Immunol. 4: 193–196.PubMedCrossRefGoogle Scholar
  11. (11).
    Dennert, G., and Hyman, R. 1980. Functional Thy-1+ cells in cultures of spleen cells from nu/nu mice. Eur. J. Immunol. 10: 583–589.PubMedCrossRefGoogle Scholar
  12. (12).
    Donohue, J.H., and Rosenberg, S.A. 1983. The fate of interleukin-2 after in vivo administration. J. Immunol. 130: 2203–2208.PubMedGoogle Scholar
  13. (13).
    Dukor, P.; Miller, J.F.A.P.; House, W.; and Allman, V. 1965. Regeneration of thymus grafts. I. Histological and cytological aspects. Transplantation 3: 639–644.PubMedCrossRefGoogle Scholar
  14. (14).
    Duprez, V.; Hamilton, B.; and Burakoff, S.J. 1982. Generation of cytolytic T lymphocytes in thymectomized, irradiated and bone marrow-reconstituted mice. J. Exp. Med. 156: 844–859.PubMedCrossRefGoogle Scholar
  15. (15).
    Elliott, E.V. 1973. A persistent lymphoid cell population in the thymus. Nature New Biol. 242: 150–152.PubMedGoogle Scholar
  16. (16).
    Ford, C.E.; Micklem, H.S.; Evans, E.P.; Gray, J.S.; and Ogden, D.A. 1966. The inflow of bone marrow cells to the thymus: studies with part-body irradiated mice injected with chromosome marked bone marrow and subjected to antigenic stimulation. Ann. NY Acad. Sci. 129: 283–296.CrossRefGoogle Scholar
  17. (17).
    Fukumoto, T.; McMaster, W.R.; and Williams, A.F. 1982. Mouse monoclonal antibodies against rat major histocompatibility antigens. Two la antigens and expression of la and class I antigens in rat thymus. Eur. J. Immunol. 12: 237–243.PubMedCrossRefGoogle Scholar
  18. (18).
    Gillis, S., and Watson, J. 1981. Interleukin-2 induction of hapten- specific cytolytic T cells in nude mice. J. Immunol. 126: 1245–1248.PubMedGoogle Scholar
  19. (19).
    Good, M.F.; Boyd, A.W.; and Nossal, G.J.V. 1983. Analysis of true anti-hapten cytotoxic clones in limit dilution microcultures after correction for “anti-self” activity: precursor frequencies, Ly-2 and Thy-1 phenotype, specificity and statistical methods. J. Immunol. 130: 2046–2055.PubMedGoogle Scholar
  20. (20).
    Good, M.F.; Pyke, K.W.; and Nossal, G.J.V. 1983. Functional clonal deletion of cytotoxic T-lymphocyte precursors in chimeric thymus produced in vitro from embryonic anlagen. Proc. Natl. Acad. Sci. USA 80: 3045–3049.PubMedCrossRefGoogle Scholar
  21. (21).
    Habu, G.; Kasai, M.; Nagai, Y.; Tamaoki, N.; Tada, T.; Herzenberg, L.A.; and Okumura, K. 1980. The glycolipid asialo G.M, as a new differentiation antigen of fetal thymocytes. J. Immunol. 125: 2284–2288.PubMedGoogle Scholar
  22. (22).
    Hammond, W.S. 1954. Origins of thymus in the chick embryo. J. Morphol. 95: 501–515.CrossRefGoogle Scholar
  23. (23).
    Haynes, B.F.; Robert-Guroff, M.; Metzgar, R.S.; Franchini, G.; Kalyanaranan, V.S.; Palker, T.J.; and Gallo, R.C. 1983. Monoclonal antibody against human T cell leukaemia virus p 19 defines a human thymic epithelial antigen acquired during ontogeny. J. Exp. Med. 157: 907–920.PubMedCrossRefGoogle Scholar
  24. (24).
    Haynes, B.F.; Warren, R.W.; Buckley, R.H.; McClure, J.E.; Goldstein, A.L.; Henderson, F.W.; Hensley, L.L.; and Eisenbarth, G.S. 1983. Demonstration of abnormalities in expression of thymic epithelial surface antigens in severe cellular immunodeficiency diseases. J. Immunnol. 130: 1182–1188.Google Scholar
  25. (25).
    Hodes, R.J. 1982. Lyt antigens as markers for functional T-cell subpopulations. Immunol. Today 3: 235–236.CrossRefGoogle Scholar
  26. (26).
    Janossy, G.; Thomas, J.A.; Goldstein, G.; and Bollum, F.T. 1981. The human thymic microenvironment. In Microenvironments in Haemopoietic and Lymphoid Differentiation. Ciba Foundation Symposium 84, pp. 193–214. London: Pitman Medical.Google Scholar
  27. (27).
    Jerne, N.K. 1971. The somatic generation of immune recognition. Eur. J. Immunol. 1: 1–9.PubMedCrossRefGoogle Scholar
  28. (28).
    Jordan, R.K. 1976. Development of sheep thymus in relation to in utero thymectomy experiments. Eur. J. Immunol. 6; 693–698.PubMedCrossRefGoogle Scholar
  29. (29).
    Kindred, B.; Corley, R.B.; and Schirrmacher, V. 1980. The relationship between alloantigen responses in nude mice injected with a low number of congenic thymus cells. Thymus 2: 83–92.PubMedGoogle Scholar
  30. (30).
    Komuro, K.; Goldstein, G.; and Boyse, E.A. 1975. Thymus re-populating capacity of cells that can be induced to differ to T cells in vitro. J. Immunol. 115: 195–198.Google Scholar
  31. (31).
    Kruisbeek, A.M.; Fultz, M.J.; Sharrow, S.D.; Singer, A.; and Mond, J.J. 1983. Early development of the T cell repertoire. In vivo treatment of neonatal mice with anti-Ia antibodies interferes with differentiation of I-restricted T cells but not K/D-restricted T cells. J. Exp. Med. 157: 1932–1946.CrossRefGoogle Scholar
  32. (32).
    Kruisbeek, A.M.; Hodes, R.J.; and Singer, A. 1981. Cytotoxic T lymphocyte responses by chimeric thymocytes, self-recognition is determined early in T cell development. J. Exp. Med. 153: 13–26.PubMedCrossRefGoogle Scholar
  33. (33).
    Kyewski, B.A., and Kaplan, H.S. 1982. Lymphoepithelial interactions in the mouse thymus: phenotypic and kinetic studies on thymic mouse cells. J. Immunol. 128: 2287–2294.PubMedGoogle Scholar
  34. (34).
    Le Douarin, N.; Jotereau, F.; Houssaint, E.; Martin, C.; and Dieterlen-Lievre, F. 1982. Ontogeny of avian lymphocytes. In The Reticuloendothelial System: Phylogeny and Ontogeny, eds. N. Cohen and M.M. Sigel, vol. 3, pp. 589–616. New York: Plenum Press.Google Scholar
  35. (35).
    Lepault, F.; Coffman, R.L.; and Weissman, I.L. 1983. Characteristics of thymus-homing bone marrow cells. J. Immunol. 131: 64–69.PubMedGoogle Scholar
  36. (36).
    Longo, D.L., and Davis, M.L. 1983. Early appearance of donor-type antigen presenting cells in the thymuses of 1200R radiation-induced bone marrow chimeras correlates with self-recognition of donor I region gene products. J. Immunol. 130: 2525–2527.PubMedGoogle Scholar
  37. (37).
    Loor, F.W., and Kindred, B. 1973. Differentiation of T-cell precursors in nude mice demonstrated by immunofluorescence of T-cell membrane markers. J. Exp. Med. 138: 1044–1055.PubMedCrossRefGoogle Scholar
  38. (38).
    Maryanski, J.L.; MacDonald, H.R.; Sordat, B.; and Cerottini, J.C. 1981. Cytolytic T lymphocyte precursor cells in congenitally athymic C57 BL/6 nu/nu mice: quantitation, enrichment, and specificity. J. Immunol. 126: 871–876.PubMedGoogle Scholar
  39. (39).
    Mathieson, B.J.; Sharrow, S.O.; Rosenberg, Y.; and Hammerling, U. 1981. Lyt l+23- cells appear in the thymus before Lyt 123+ cells. Nature 289: 179–181.PubMedCrossRefGoogle Scholar
  40. (40).
    Miller, J.F.A.P. 1979. Experimental thymology has come of age. Thymus 1 3–25.PubMedGoogle Scholar
  41. (41).
    Miller, J.F.A.P., and Osoba, D. 1967. Current concepts of the immunological function of the thymus. Physiol. Rev. 47: 437–487.PubMedGoogle Scholar
  42. (42).
    Miller, R.G.; Derry, H.R.; and Garjeant, B.J. 1983. The extent of self MHC restriction of cytotoxic T cells in nude mice varies from mouse to mouse. J. Immunol. 130: 63–68.PubMedGoogle Scholar
  43. (43).
    Mitchison, N.A., and Pettersson, G. 1983. Does clonal selection occur among T cells ? Ann. Immunol. (Inst. Pasteur) 134D: 37–45.CrossRefGoogle Scholar
  44. (44).
    Morrissey, P.J.; Kruisbeek, A.M.; Sharrow, S.O.; and Singer, A. 1982. Tolerance of thymic cytotoxic T lymphocytes to allogeneic H-2 determinants encountered pre-thymically: evidence of expression of anti-H2 receptors prior to entry to the thymus. Proc. Natl. Acad. Sci. USA 79: 2003–2007.PubMedCrossRefGoogle Scholar
  45. (45).
    Muraoka, S., and Miller, R.S. 1983. Cells in immune fetal liver and in lymphoid colonies grown from fetal liver can suppress generation of cytotoxic T lymphocytes directed against their self antigens. J. Immunol. 131: 45–49.PubMedGoogle Scholar
  46. (46).
    Owen, F.L. 1982. Products of the IgT-C region of chromosome 12 are maturational markers for T cells. Sequence of appearance in immunocompetent T cells parallels ontogenetic appearance of T thyd, T indd, and Tsud. J. Exp. Med. 156: 703–718.PubMedCrossRefGoogle Scholar
  47. (47).
    Owen, F.L. 1983. Tpre, a new alloantigen encoded in the IgT-C region of chromosome 12, is expressed on bone marrow of nude mice, fetal T cell hybrids and fetal thymus. 157: 419–432.PubMedCrossRefGoogle Scholar
  48. (48).
    Owen, J.J.T., and Jenkinson, E.J. 1981. Embryology of the lymphoid system. Progr. Allergy 29: 1–34.Google Scholar
  49. (49).
    Owen, J.J.T.; Jenkinson, E.J.; and Kingston, R. 1983. The ontogeny of T lymphocytes. Ann. Immunol. (Inst. Pasteur) 134D: 115–122.Google Scholar
  50. (50).
    Piguet, P.F.; Irle, C.; Kollatte, E.; and Vassalli, P. 1981. Post-thymic T lymphocyte maturation during ontogenesis. J. Exp. Med. 154: 581–584.PubMedCrossRefGoogle Scholar
  51. (51).
    Ranges, S.E.; Goldstein, G.; Boyse, E.A.; and Schield, M.P. 1982. T cell development in normal and thymopentin-treated nude mice. J. Exp. Med. 156: 1057–1064.PubMedCrossRefGoogle Scholar
  52. (52).
    Rouse, R.V., and Weissman, I.L. 1981. Microanatomy of the thymus: its relationship to T cell differentiation. In Microenvironments in Haemopoietic and Lymphoid Differentiation. Ciba Foundation Symposium 84, pp. 161–177. London: Pitman Medical.Google Scholar
  53. (53).
    Scollay, R. 1982. Thymus cell migration: cells migrating from thymus to peripheral lymphoid organs have a “mature” phenotype. J. Immunol. 128: 1566–1577.PubMedGoogle Scholar
  54. (54).
    Sharrow, S.O.; Mathieson, B.J.; and Singer, A. 1981. Cell surface appearance of unexpected host MHC determinants on thymocytes from radiation bone marrow chimeras. J. Immunol. 126: 1327–1335.PubMedGoogle Scholar
  55. (55).
    Shortman, K. 1977. The pathway of T-cell development within the thymus. In Progress in Immunology III, eds. T.E. Mandel, C. Cheers, C.S. Hosking, I.F.C. McKenzie, and G.J.V. Nossal, pp. 197–205. New York: Elsevier/North-Holland.Google Scholar
  56. (56).
    Shortman, K.; Wilson, A.; Scollay, R.; and Chen, W-F. 1983. Development of large granular lymphocytes with anomalous non-specific cytotoxicity in clones derived from Ly-2+ T cells. Proc. Natl. Acad. Sci. USA 80: 2728–2732.PubMedCrossRefGoogle Scholar
  57. (57).
    Stutman, O. 1978. Intrathymic and extrathymic T cell maturation. Immunol. Rev. 42: 138–184.CrossRefGoogle Scholar
  58. (58).
    Teh, H.S.; Bennink, J.; and von Boehmer, H.V. 1982. Selection of the T cell repertoire during ontogeny: limiting dilution analysis. Eur. J. Immunol. 12: 887–892.PubMedCrossRefGoogle Scholar
  59. (59).
    Van Ewijk, W.; Jenkinson, E.J.; and Owen, J.J.T. 1982. Detection of Thy-1, T-200, Lyt 1 and Lyt 2 bearing cells in the developing lymphoid organs of the mouse embryo in vivo and in vitro. Eur. J. Immunol. 12; 262–271.PubMedCrossRefGoogle Scholar
  60. (60).
    Van Ewijk, W.; Rouse, R.V.; and Weissman, I.L. 1980. Distribution of H-2 microenvironments in the mouse thymus. Immuno-electron microscopic identification of I-A and H-2K bearing cells. J. Histochem. Cytochem. 28: 1089–1099.PubMedCrossRefGoogle Scholar
  61. (61).
    Von Boehmer, H.; Bennink, J.; Teh, H.S.; and Haas, W. 1983. Selection of the T-cell repertoire during ontogeny. Ann. Immunol. (Inst. Pasteur) 134D: 17–24.Google Scholar
  62. (62).
    Wallis, V.; Leuchars, E.; Chwalinski, S.; and Davies, A.J.S. 1975. On the sparse seeding of bone marrow and thymus in radiation chimaeras. Transplantation 19: 2–11.PubMedCrossRefGoogle Scholar
  63. (63).
    Wei-Feng, C.; Scollay, R.; and Shortman, K. 1982. The functional capacity of thymus subpopulations: limit-dilution analysis of all precursors of cytotoxic lymphocytes and of all T cells capable of proliferation in subpopulations separated by the use of peanut agglutinin. J. Immunol. 129: 18–24.PubMedGoogle Scholar
  64. (64).
    Weissman, I.L. 1967. Thymus cell migration. J. Exp. Med. 126: 291–297.PubMedCrossRefGoogle Scholar
  65. (65).
    Zielinski, C.C.; Waksal, S.D.; and Datta, S.K. 1982. Thymic epithelium is programmed to induce preleukemic changes in retrovirus expression and thymocyte differentiation in leukemia susceptible mice: studies on bone marrow and thymic chimeras. J. Immunol. 129: 882–889.PubMedGoogle Scholar
  66. (66).
    Zinkernagel, R.M. 1978. Thymus and lymphohaemopoietic cells: their role in T-cell maturation in selection of T cells’ H-2 restriction specificity and in H-2 linked gene control. Immunol. Rev. 42: 224–270.PubMedCrossRefGoogle Scholar
  67. (67).
    Zinkernagel, R.M. 1982. Selection of restriction specificities of virus-specific cytolotoxic T cells in the thymus: no evidence for a crucial role of antigen-presenting cells. J. Exp. Med. 156: 1842–1847.PubMedCrossRefGoogle Scholar

Copyright information

© Dr. S. Bernhard, Dahlem Konferenzen, Berlin 1985

Authors and Affiliations

  • J. J. T. Owen
    • 1
  1. 1.Dept. of AnatomyUniversity of BirminghamBirminghamEngland

Personalised recommendations