Advertisement

Thymic Ontogeny and the T-Cell Receptor Genes

  • Nicolette Caccia
  • Rosanne Spolski
  • Tak W. Mak

Abstract

The mammalian immune system is composed of a number of well-regulated cells and their products, which provide an effective defense against infection by viruses, bacteria, and parasites. This system can be broadly divided into two interacting components: nonspecific immunity, which is effected by cells such as macrophages and natural killer cells, and specific immunity, which provides the fine tuning and is mediated by B and T lymphocytes. Specific immunity can be further divided into humoral and cell-mediated responses. The humoral response is mediated by B lymphocytes, which secrete immunoglobulins, antigen-specific molecules involved in a number of immune reactions leading to the elimination of antigen (Davies and Metzger, 1983; Honjo, 1983). Regulation of the humoral response and mediation of the cellular response is provided by T lymphocytes, which, unlike B cells, respond exclusively to foreign antigens on the surface of cells, and only recognize these antigens in the context of self class I or class II products encoded by the major histocompatibility complex (MHC). Class I products are found on all cells within an organism, while class II MHC products are expressed only on lymphoid cells and macrophages, and the inability of T cells to respond to antigen except in the context of these products is known as MHC restriction (Zinkernagel and Doherty, 1974; Katz et al., 1973; Rosenthal and Shevach, 1973).

Keywords

Major Histocompatibility Complex Athymic Mouse Major Histocompatibility Complex Restriction Double Negative Cell Thymic Leukemia 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Acuto, O., Hussey, R.E., Fitzgerald, K. A., Protentis, J. P., Meuer, S. C., Schlossman, S. F., and Reinherz, E. L., 1985, The human T cell receptor: appearance in ontogeny and biochemical relationship of α and β subunits on IL-2 dependent clones and T cell tumors, Cell 34:717–726.CrossRefGoogle Scholar
  2. Bevan, M. J., 1977, In a radiation chimaera, host H-2 antigens determine immune responsiveness of donor cytotoxic cells, Nature 269:417–418.PubMedCrossRefGoogle Scholar
  3. Bevan, M. J., 1983, Thymic education, in T Lymphocytes Today (J. R. Inglis, ed.), pp. 38–41, Elsevier Science Publishers, Amsterdam.Google Scholar
  4. Bevan, M. J., and Fink, P. J., 1978, The influence of thymus H-2 antigen on the specificity of maturing killer and helper cells, Imm. Rev. 42:3–19.CrossRefGoogle Scholar
  5. Born, W., Rathburn, G., Tucker, P., Marrack, P., and Kappler, J., 1986, Synchronized rearrangement of T cell γ and β chain genes during fetal thymocyte development, Science 234:479–482.PubMedCrossRefGoogle Scholar
  6. Born, W., Yague, J., Palmet, E., Kappler, J., and Marrack, P., 1985, Rearrangement of T-cell receptor β-chain genes during T cell development, Proc. Natl. Acad. Sci. U.S.A. 82:2925–2929.PubMedCrossRefGoogle Scholar
  7. Ceredig, R., Dialynis, D. P., Fitch, F. W., and MacDonald, H. R., 1983a, Precursors of T cell growth factor producing cells in the thymus, JEM 158:1654–1671.CrossRefGoogle Scholar
  8. Ceredig, R., MacDonald, H. R., and Jenkinson, E. J., 1983b, Flow microfluorometric analysis of mouse thymus development in vivo and in vitro, Eur. J. Immunol. 13:185–190.PubMedCrossRefGoogle Scholar
  9. Chien, Y., Becker, D., Lindsten, T., Okamura, M., Cohen, D., and Davis, M., 1985, A third type of murine T-cell receptor gene, Nature 312:31–36.CrossRefGoogle Scholar
  10. Collins, M. K. L., Tanigawa, G., Kissonherghis, A.-M., Ritter, M., Price, K. M., Tonegawa, S., and Owen, M.J., 1985, Regulation of T-cell receptor gene expression in human T-cell development, Proc. Natl. Acad. Sci. USA 82:4503–4507.PubMedCrossRefGoogle Scholar
  11. Davies D. R., and Metzger, H., 1983, Structural basis of antibody function, Annu. Rev. Immunol. 1:63–86.CrossRefGoogle Scholar
  12. Enzine, S., Weissman, I. L., and Rouse, R. V., 1984, Bone marrow cells give rise to distinct cell clones within the thymus, Nature 309:629–631.CrossRefGoogle Scholar
  13. Fink, P. J., and Bevan, M. J., 1978, H-2 antigens of the thymus determine lymphocyte specificity, J. Exp. Med. 148:766–775.PubMedCrossRefGoogle Scholar
  14. Fink, P. J., Gallatin, W. M., Reichert, R. A., Butcher, E. C., and Weissman, I. L., 1985, Homing receptor-bearing thymocytes, an immunocompetent cortical subpopulation, Nature 313: 233–235.PubMedCrossRefGoogle Scholar
  15. Haars, R., Kronenberg, M., Owen, F., Gallatin, M., Weissman, I., and Hood, L., 1986, Rearrangement and expression of T-cell antigen receptor and γ chain genes during thymic differentiation, J. Exp. Med. 164:1–24.PubMedCrossRefGoogle Scholar
  16. Habu, S., and Okamura, K., 1984, Cell surface antigen marking the stages of murine T cell ontogeny and its functional subsets, Immunol. Rev. 82:117–139.PubMedCrossRefGoogle Scholar
  17. Habu, S., Okamura, K., Diamentstein, T., and Shevach, E. M., 1985, Expression of interleukin 2 receptor on murine fetal thymocytes, Eur. J. Immunol. 15:456–460.PubMedCrossRefGoogle Scholar
  18. Hedrick, S. M., Cohen, D. I., Nielsen, E. A., and Davis M. M., 1984a, Isolation of cDNA clones encoding T cell specific membrane-associated proteins, Nature 308:149–152.PubMedCrossRefGoogle Scholar
  19. Hedrick, S. M., Neilsen, E. A., Kavaler, J., Cohen, D. I., and Davis, M. M., 1984b, Sequence relationships between putative T-cell receptor polypeptides and immunoglobulins, Nature 308:153–158.PubMedCrossRefGoogle Scholar
  20. Heilig, J. S., Glimcher, L. H., Kranz, D. M., Clayton, L. K., Greenstein, J. L., Saito, H., Maxam, A. M., Burakoff, S. J., Eisen, H. N., and Tonegawa, S., 1985, Expression of the T-cell specific γ gene is unnecessary in T cells recognizing class II MHC determinants, Nature 317:68–70.PubMedCrossRefGoogle Scholar
  21. Honjo, T., 1983, Immunoglobulin genes, Annu. Rev. Immunol. 1:499–528.PubMedCrossRefGoogle Scholar
  22. Hunig, T., 1983, T cell function and specificity in athymic mice, in: T Lymphocytes Today (J. R. Inglis, ed.), pp. 42–45, Elsevier Science Publisher, Amsterdam.Google Scholar
  23. Iwamoto, I., Ohashi, P., Walker, C., Rupp, F., Yoho, H., Hengartner, H., and Mak, T. W., 1986, The murine γ chain genes in B10 mice: Sequence and expression of new constant and variable genes, J. Exp. Med. 163:1203–1212.PubMedCrossRefGoogle Scholar
  24. Kappler, J., Kubo, R., Haskins, K., Hannum, C., Marrack, P., Pigeon, M., McIntyre, B., Allison, J., and Trowbridge, I., 1983a, the MHC-restricted antigen receptor on T cells: identification of constant and variable peptides, Cell 35:295–302.PubMedCrossRefGoogle Scholar
  25. Kappler, J., Kubo, R., Haskins, K., White, J., and Marrack, P., 1983b, The mouse T cell receptor: comparison of MHC-restricted receptors on two T cell hybridomas, Cell 34:727–737. PubMedCrossRefGoogle Scholar
  26. Katz, D. H., Hamaoka, T., and Benacerraf, B., 1973, Cell interactions between histoincompatible T and B lymphocytes, J. Exp. Med. 137:1405–1418.PubMedCrossRefGoogle Scholar
  27. Kishihara, K., Yoshikai, Y., Matsuzakai, G., Mak, T. W., Nomoto, K., 1987, Functional α and β chain T cell receptor messages can be detected in old, but not young, athymic mice, Eur. J., Immunol. (in press).Google Scholar
  28. Lake, J. P., Andrew, M. E., Pierce, C. W., and Braciale, T. J., 1980, Sendai virus-specific, H-2 restricted cytotoxic T lymphocyte responses of nude mice grafted with allogeneic or semi-allogeneic thymus glands, J. Exp. Med. 152:1805–1810.PubMedCrossRefGoogle Scholar
  29. LeDourain, N. M., and Jotereau, F. V., 1975, Tracing of cells in the avian thymus through embryonic life in interspecific chimeras, J. Exp. Med. 142:17–40.CrossRefGoogle Scholar
  30. Lu, C. Y., Beller, D. I., and Unanue, E. R., 1980, During ontogeny, Ia bearing accessory cells are found early in the thymus, but late in the spleen, Proc. Natl. Acad. Sci. USA 77:1597–1601.PubMedCrossRefGoogle Scholar
  31. McIntyre, B.W., and Allison, J. P., 1983, The mouse T cell receptor: structural heterogeneity of molecules of normal T cells defined by xenoantiserum, Cell 34:739–746.PubMedCrossRefGoogle Scholar
  32. Mathieson, B. J., Sharrow, S. O., Rosenberg, Y., and Hammerling, U., 1981, Lyt1+23 cells appear in the thymus before Lyt 123+ cells, Nature 289:179–181.PubMedCrossRefGoogle Scholar
  33. Minowada, J., Koshiba, H., Sagawa, K., Kubonishi, I., Lok, M. S., Tatsumi, E., Han, T., Srivastava, B. I. S., and Ohnuma, T., 1981, Marker profiles of human leukemia and lymphoma cell lines, J. Cancer Res. Clin. Oncol. 101:91–100.PubMedCrossRefGoogle Scholar
  34. Minowada, J., Minato, K., Srivastava, B. I. S., Nakazawa, S., Kubonishi, I., Tatsumi, E., Ohnuma, T., Ozer, H., Freeman, A. I., Henderson, E. S., and Gallo, R. C., 1982. A model scheme of human hematopoietic cell differentiation as determined by leukemia-lymphoma study: T-cell lineages, in: Current Concepts in Human Immunology and Cancer Immunomodulation (Serrou, B., Rosenfeld, C., Daniels, J. C., and Saunders, J. P., eds.), Elsevier Biomedical Press B. V.Google Scholar
  35. Minowada, J., Minato, K., Tatsumi, E., Sugimoto, T., Nakazawa, S., Ohnuma, T., Kubonishi, I., Miyoshi, I., Frankel, A., and Gallo, R. C., 1983. A model scheme for human hematopoietic cell differentiation as determined by multiple markers of leukemia-lymphomas, In: Haematology and Blood Transfusion, Vol. 28 (Neth, R., Gallo, R., Greaves, M., Moore, O., and Winkler, F., eds.), pp. 348–350, Springer-Verlag, Berlin.Google Scholar
  36. Nagasawa, K., and Mak, T.W., 1980, Phorbol esters induce differentiation in human malignant T lymphoblasts, Proc. Natl. Acad. Sci. USA 77:2964–2968.PubMedCrossRefGoogle Scholar
  37. Ohashi, P., Mak, T. W., Van den Elsen, P., Yanagi, Y., Yoshikai, Y., Calman, A. F., Terhorst, C., Stobo, J. D., and Weiss, A., 1985, Reconstitution of an active T3/T cell antigen receptor in human T cells by DNA transfer, Nature 316:602–606.CrossRefGoogle Scholar
  38. Raulet, D. H., Garman, R. D., Saito, H., and Tonegawa, S., 1985, Developmental regulation of T-cell receptor gene expression, Nature 314:103–107.PubMedCrossRefGoogle Scholar
  39. Reichert, R. A., Gallatin, W. M., Butcher, E. C., and Weissman, I. L., 1984, A homing receptor-bearing cortical thymocyte subset: implications for cortisone-resistant thymocytes, Cell 38:89–99.PubMedCrossRefGoogle Scholar
  40. Reinhertz, E. L., Kung, P. C., Goldstein, G., Levey, R. H., and Schlossman, S. F., 1980, Discrete stages of human intrathymic differentiation: Analysis of normal thymocytes and leukemia lymphoblasts of T-cell lineage, Proc. Natl. Acad. Sci. U.S.A. 77:1588–1592.CrossRefGoogle Scholar
  41. Roehm, N., Herron, L., Cambier, J., DiGuisto, D., Haskins, K., Kappler, J., and Marrack, P., 1984, The major histocompatability complex-restricted antigen receptor on T cells: Distribution in thymus and peripheral blood T cells, Cell 38:577–584.PubMedCrossRefGoogle Scholar
  42. Rosenthal, A. S., and Shevach, E. M., 1973, Function of macrophages in antigen recognition by guinea pig T lymphocytes, J. Exp. Med. 138:1194–1212.PubMedCrossRefGoogle Scholar
  43. Royer, H. D., Acuto, A., Fabbi, M., Tizzard, R., Rammachandran, K., Smart, J., and Reinherz, E. L., 1984, Genes encoding the Ti β subunit of the antigen/MHC receptor undergo rearrangement during intrathymic ontogeny prior to surface T3-Ti expression, Cell 39:261–266.PubMedCrossRefGoogle Scholar
  44. Royer, H. D., Ramarli, D., Acuto, O., Campen, T. J., and Reinherz, E. L., 1985, Genes encoding the T-cell receptor α and β subunits are transcribed in an ordered manner during intrathymic ontogeny, Proc. Natl. Acad. Sci. USA 82:5510–5514.PubMedCrossRefGoogle Scholar
  45. Saito, H., Kranz, D., Takagaki, Y., Hayday, A., Eisen, H., and Tonegawa, S., 1984a, A third rearranged and expressed gene in a clone of cytotoxic T lymphocytes, Nature 312:36–40.PubMedCrossRefGoogle Scholar
  46. Saito, H., Kranz, D. M., Takagaki, Y., Hayday, A., Eisen, A. C., Tonegawa, S., 1984b, Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences, Nature 309:757–762.PubMedCrossRefGoogle Scholar
  47. Sangster, B., Minowada, J., Suci-Foca, N., Minden, M., and Mak, T. W., 1986, Rearrangement and expression of the α, β and γ T cell receptor genes in human leukemias and functional T cells, J. Exp. Med. 163:1491–1507.PubMedCrossRefGoogle Scholar
  48. Scollay, R., 1983, Intrathymic events in the differentiation of T lymphocytes: a continuing enigma, in: T Lymphocytes Today (J. R. Inglis, ed.), pp. 52–56, Elsevier Science Publishers, Amsterdam.Google Scholar
  49. Scollay, R. G., Butcher, E. C., and Weissman, I. L., 1980, Quantitative aspects of cellular traffic from the thymus to the periphery in mice, Eur. J. Immunol. 10:210–218.PubMedCrossRefGoogle Scholar
  50. Scollay, R., Chen, W.-F., and Shortman, K., 1984a, The functional capabilities of cells leaving the thymus, J. Immunol. 132:25–30.PubMedGoogle Scholar
  51. Scollay, R., Wilson, A., and Shortman, K., 1984b, Thymus cell migration: analysis of thymus emigrants with markers that distinguish medullary thymocytes from peripheral T cells, J. Immunol. 132:1089–1094.PubMedGoogle Scholar
  52. Sim, G. K., Yague, J., Nelson, J., Marrack, P., Palmer, E., Augustin, A., and Kappler, J., 1984, Primary structure of human T-cell receptor α chain, Nature 312:771–775.PubMedCrossRefGoogle Scholar
  53. Snodgrass, H. R., Dembic, Z., Steinmetz, M., von Boehmer, H., 1985a, Expression of T-cell antigen receptor genes during fetal development in the thymus, Nature 313:232–233.CrossRefGoogle Scholar
  54. Snodgrass, H. R., Kisielow, P., Kiefer, M., Steinmetz, M., and von Boehmer, H., 1985b, Ontogeny of the T-cell antigen receptor within the thymus, Nature 313:592–595.PubMedCrossRefGoogle Scholar
  55. Takacs, L., Osawa, H., and Diamentstein, T., 1984, Detection and localization by the monoclonal anti-interleukin-2 receptor antibody AMT-13 of IL2 receptor-bearing cells in the developing thymus of the mouse embryo and in the thymus of cortisone-treated mice, Eur. J. Immunol. 14:1152–1156.PubMedCrossRefGoogle Scholar
  56. Toyonaga, B., Yanagi, Y., Suciu-Foca, N., Minden, M., and Mak, T. W., 1984, Rearrangements of T cell receptor gene YT35 in human DNA from thymic leukemia T cell lines and functional T cell clones, Nature 311:385–387.PubMedCrossRefGoogle Scholar
  57. van Ewijk, W., Jenkinsson, E. J., 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
  58. Waldmann, H., Pope, H., Brent, L., and Bighouse, K., 1978, Influence of the major histocompatibility complex on lymphocyte interactions in antibody formation, Nature 274:166–168.PubMedCrossRefGoogle Scholar
  59. Widmer, M. D., MacDonald, H. R., and Cerottini, J. C., 1981, Limiting dilution analysis of alloantigen-reactive T lymphocytes, VI, Ontogeny of cytolytic T lymphocyte precursors in the thymus, Thymus 2:245–255.PubMedGoogle Scholar
  60. Winoto, A., Mjolsness, S., and Hood, L., 1985, Genomic organization of the genes encoding mouse T-cell receptor α chain, Nature 316:832–836.PubMedCrossRefGoogle Scholar
  61. Yanagi, Y., Yoshikai, Y., Leggett, K., Clark, S. P., Aleksander, I., Mak, T. W., 1984, A human T cell specific cDNA clone encodes a protein having extensive homology to immunoglobulin chains, Nature 308:145–149.PubMedCrossRefGoogle Scholar
  62. Yoshikai, Y., Anatoniou, D., Clark, S. P., Yanagi, Y., Sangster, R., Van den Elsen, P., Terhorst, C., and Mak, T. W., 1984a, Sequence and expression of transcripts of the human T-cell receptor β-chain genes, Nature 312:521–524.PubMedCrossRefGoogle Scholar
  63. Yoshikai, Y., Clark, S. P., Taylor, S., Sohn, U., Wilson, B., Minden, M., and Mak, T. W., 1985, Organization and sequences of the variable, joining and constant region genes of the human T cell receptor a chain, Nature 31:837–840.CrossRefGoogle Scholar
  64. Yoshikai, Y., Reis, M. D., and Mak, T. W., 1986, Athymic mice express a high level of functional γ chain, but drastically reduced levels of α and β chain T cell receptor messages, Nature 324:482–485.PubMedCrossRefGoogle Scholar
  65. Yoshikai, Y., Yanagi, Y., Suciu-Foca, N., and Mak, T. W., 1984b, Presence of T cell receptor mRNA in functionally distinct T cells and elevation during intrathymic differentiation, Nature 310:506–508.PubMedCrossRefGoogle Scholar
  66. Zauderer, M., Iwamoto, L, and Mak, T. W., 1986, Gamma gene expression in autoreactive helper T cells, J. Exp. Med. 163:1314–1318.PubMedCrossRefGoogle Scholar
  67. Zinkernagel, R. M., Althage, A., Waterfield, E., Kindred, B., Welsh, R. M., Callahan, G., and Pincetl, P., 1980, Restriction specificities, alloreactivity, and allotolerance expressed by T cells from nude mice reconstituted with H-2 compatible or incompatible thymus grafts, J. Exp. Med. 151:376–399.PubMedCrossRefGoogle Scholar
  68. Zinkernagel, R. M., and Doherty, P. C., 1974, Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system, Nature 248:701–702.PubMedCrossRefGoogle Scholar
  69. Zinkernagel, R. M., Gallahan, G. N., Althage, A., Cooper, S., Klein, P. A., and Klein, J., 1978, On the thymus in the differentiation of H-2 self recognition by T cells: Evidence for dual recognition? J. Exp. Med. 147:882–896.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Nicolette Caccia
    • 1
  • Rosanne Spolski
    • 1
  • Tak W. Mak
    • 1
  1. 1.Department of Medicine and Medical Biophysics, Ontario Cancer InstituteUniversity of TorontoTorontoCanada

Personalised recommendations