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.
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References
Ando, I., and Hurme, M. 1981. Self-MHC-restricted cytotoxic T-cell responses without thymic influence. Nature 289: 494–495.
Bach, J-F., and Goldstein, G. 1980. Newer concepts of thymic hormones. Thymus 2: 1–4.
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.
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.
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.
Beller, D.I., and Unanue, E.R. 1980. I-A antigens and antigen-presenting function of thymic macrophages. J. Immunol. 124: 1443–1450.
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.
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.
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.
Cordier, A.C., and Heremans, J.F. 1975. Nude mouse embryo. Ectodermal nature of the primordial thymic defect. Scand. J. Immunol. 4: 193–196.
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.
Donohue, J.H., and Rosenberg, S.A. 1983. The fate of interleukin-2 after in vivo administration. J. Immunol. 130: 2203–2208.
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.
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.
Elliott, E.V. 1973. A persistent lymphoid cell population in the thymus. Nature New Biol. 242: 150–152.
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.
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.
Gillis, S., and Watson, J. 1981. Interleukin-2 induction of hapten- specific cytolytic T cells in nude mice. J. Immunol. 126: 1245–1248.
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.
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.
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.
Hammond, W.S. 1954. Origins of thymus in the chick embryo. J. Morphol. 95: 501–515.
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.
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.
Hodes, R.J. 1982. Lyt antigens as markers for functional T-cell subpopulations. Immunol. Today 3: 235–236.
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.
Jerne, N.K. 1971. The somatic generation of immune recognition. Eur. J. Immunol. 1: 1–9.
Jordan, R.K. 1976. Development of sheep thymus in relation to in utero thymectomy experiments. Eur. J. Immunol. 6; 693–698.
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.
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.
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.
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.
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.
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.
Lepault, F.; Coffman, R.L.; and Weissman, I.L. 1983. Characteristics of thymus-homing bone marrow cells. J. Immunol. 131: 64–69.
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.
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.
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.
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.
Miller, J.F.A.P. 1979. Experimental thymology has come of age. Thymus 1 3–25.
Miller, J.F.A.P., and Osoba, D. 1967. Current concepts of the immunological function of the thymus. Physiol. Rev. 47: 437–487.
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.
Mitchison, N.A., and Pettersson, G. 1983. Does clonal selection occur among T cells ? Ann. Immunol. (Inst. Pasteur) 134D: 37–45.
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.
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.
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.
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.
Owen, J.J.T., and Jenkinson, E.J. 1981. Embryology of the lymphoid system. Progr. Allergy 29: 1–34.
Owen, J.J.T.; Jenkinson, E.J.; and Kingston, R. 1983. The ontogeny of T lymphocytes. Ann. Immunol. (Inst. Pasteur) 134D: 115–122.
Piguet, P.F.; Irle, C.; Kollatte, E.; and Vassalli, P. 1981. Post-thymic T lymphocyte maturation during ontogenesis. J. Exp. Med. 154: 581–584.
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.
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.
Scollay, R. 1982. Thymus cell migration: cells migrating from thymus to peripheral lymphoid organs have a “mature” phenotype. J. Immunol. 128: 1566–1577.
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.
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.
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.
Stutman, O. 1978. Intrathymic and extrathymic T cell maturation. Immunol. Rev. 42: 138–184.
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.
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.
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.
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.
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.
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.
Weissman, I.L. 1967. Thymus cell migration. J. Exp. Med. 126: 291–297.
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.
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.
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.
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© 1985 Dr. S. Bernhard, Dahlem Konferenzen, Berlin
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Owen, J.J.T. (1985). Differentiation of T Lymphocytes. In: Weissman, I.L. (eds) Leukemia. Life Sciences Research Reports, vol 30. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-69722-7_8
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DOI: https://doi.org/10.1007/978-3-642-69722-7_8
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