Abstract
The thymus has two important roles in controlling the specificity of T lymphocytes. First, T cells differentiating in the thymus are rendered tolerant of ‘self’ antigens, particularly antigens encoded by the major histocompatibility complex, the H–2 complex in mice1. Second, the thymus imbues T cells with the property of H–2-restricted recognition of antigen, that is, the capacity of T cells to react with foreign antigens presented in association with self H–2 gene products2,3. Until recently it has generally been assumed that self-tolerance and H–2-restricted specificity both reflect early T-cell contact with self H–2 determinants expressed on thymic epithelial cells. Recent evidence suggests, however, that intrathymic cells of the macrophage/dendritic cell (MØ/DC) lineage also have a role in shaping T-cell specificity4–7. In particular, it has been found that the tolerance to graft-type H–2 determinants which normally ensues when T cells differentiate in an H–2-different thymus fails to occur when the thymus is pretreated with deoxyguanosine (dGuo)6,7,a procedure that selectively destroys MØ/DC but spares epithelial cells8. In contrast to these findings on tolerance induction, evidence is presented here that dGuo-treated thymus grafts do imprint T cells with H–2-restricted specificity for antigen. It appears, therefore, that induction of tolerance and H–2 restriction are controlled by different cells in the thymus.
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References
Klein, J. (ed.) Immunology: The Science of Self-Nonself Discrimination 1–687 (Wiley, New York, 1982).
Zinkernagel, R. M. Immun. Rev. 42, 224–270 (1978).
Bevan, M. J. & Fink, P. J. Immun. Rev. 42, 3–19 (1978).
Longo, D. L. & Schwartz, R. H. Nature 287, 44–46 (1980).
Longo, D. L. & Davis, M. L. J. Immun. 130, 2525–2527 (1983).
Ready, A. R., Jenkinson, E. J., Kingston, R. & Owen, J. J. T. Nature 310, 231–233 (1984).
von Boehmer, H. & Schubiger, K. Eur. J. Immun. 14, 1048–1052 (1983).
Jenkinson, E.J., Franchi, L., Kingston, R. & Owen, J.J.T. Eur. J. Immun. 12, 583–587 (1982).
Sprent, J. J. exp. Med. 147, 1838–1842 (1978).
Kappler, J. W. & Marrack, P. J. exp. Med. 148, 1510–1522 (1978).
Singer, A., Hathcock, K. S. & Hodes, R. J. J. exp. Med. 153, 1286–1301 (1981).
von Boehmer, H. & Haas, W. J. exp. Med. 150, 1134–1142 (1979).
Bevan, M. J. Nature 269, 417–418 (1977).
Zinkernagel, R. M. et al. J. exp. Med. 147, 882–896 (1978).
Matzinger, P. & Mirkwood, G. J. exp. Med. 148, 84–92 (1978).
Kruisbeek, A. M., Sharrow, S. O. & Singer, A. J. Immun. 130, 1027–1032 (1983).
Wagner, H. et al. J. exp. Med. 153, 1517–1532 (1981).
Corradin, G., Etlinger, H. M. & Chiller, J. M. J. Immun. 119, 1048–1053 (1977).
Robinson, J. H. J. Immun. 130, 1592–1595 (1983).
Barclay, A. N. & Mayrhofer, G. J. exp. Med. 153, 1666–1671 (1981).
Kyewski, B. A., Fatham, C. G. & Kaplan, H. S. Nature 308, 196–199 (1984).
Jordan, R.K., Bentley, A.L., Perry, G.A. & Crouse, D.A. J. Immun. 134, 2155–2160 (1985).
Zinkernagel, R. M. J. exp. Med. 156, 1842–1847 (1982).
Fink, P. J. & Bevan, M. J. in Recognition and Regulation in Cell Mediated Immunity (eds Watson, J. D. & Marbrook, J.) 107–125 (Dekker, New York, 1985).
Robinson, J. H. & Owen, J. J. T. Nature 271, 758–760 (1978).
Good, M.F., Pyke, K.W. & Nossal, G.J.V. Proc. natn. Acad. Sci. U.S.A. 80, 3045–3049 (1983).
Jenkinson, E.J., Jhittay, P., Kingston, R. & Owen, J.J.T. Transplantation 39, 331–333 (1985).
Jordan, R. K., Robinson, J. H., Hopkinson, N. A., House, K. C. & Bentley, A. L. Nature 314, 454–456 (1985).
Nathanson, S. D., Zamfirescu, P. L., Drew, S. I. & Wilbur, S. J. immun. Meth. 18, 225–234 (1977).
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Lo, D., Sprent, J. Identity of cells that imprint H–2-restricted T-cell specificity in the thymus. Nature 319, 672–675 (1986). https://doi.org/10.1038/319672a0
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DOI: https://doi.org/10.1038/319672a0
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