Abstract
BECAUSE of positive and negative selection to molecules of the major histocompatibility complex (MHC)1, only a small propor-tion of the massive numbers of T cells generated in the thymus are selected for export2,3. Immature thymocytes have a rapid turnover2, and it has long been assumed that most thymocytes die i/i siVw4,5, presumably from apoptosis6. This has yet to be proved, however, and conventional staining techniques have shown only minimal evidence of cell death in the normal thymus7,8. Using a method for detecting cells with DNA strand breaks, we now present direct evidence for apoptosis in the normal thymus. In sections of thymus from adult mice, apoptotic cells are scattered throughout the cortex and are engulfed locally by F4/80+ macrophages. Apoptosis in the thymic cortex is not reduced in MHC-deficient mice, which suggests that T-cell death is primarily a reflection of lack of positive selection rather than negative selection. Direct evidence for apoptosis due to negative selection was obtained by crossing a Vβ5 transgenic line9 to I–E+ and I–E- mice: I–E+ mice are known to eliminate Vβ5+ T cells in the thymus whereas I–E- mice do not10. In marked contrast to I–E- mice, the medulla of I–E+ Vβ5 transgenic mice contains dense aggregates of apoptotic cells; these cells are engulfed by a distinct population of F4/80- MAC-3+ macrophages. Negative selection of Vβ5+ cells is thus restricted to the medulla.
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References
Robey, E. & Fowlkes, B. J. A. Rev. Immun. 12, 675–705 (1994).
Shortman, K., Egerton, M., Spangrude, G. J. & Scollary, R. Semin. Immun. 2, 3–12 (1990).
Tough, D. & Sprent, J. J. exp. Med. 179, 1127–1135 (1994).
Scollary, R. & Shortman, K. in Recognition and Regulation in Cell-mediated Immunity (eds Watson, J. D. & Marbrook, J.) 3–20 (Dekker, New York, 1985).
Metcalf, D. in Ciba Symposium of the Thymus: Experimental and Clinical Studies (eds Wolstenholme, G. E. W. & Porter, P.) 242–263 (Churchill, London, 1966).
Kerr, J. F. R., Wyllie, A. H. & Currie, A. R. Br. J. Cancer 26, 239–257 (1972).
Saint-Marie, G. & Peng, F. S. Rev. Can. Biol. 30, 51–78 (1970).
Kendall, M. D. Immun. Today 5, 286–287 (1984).
Fink, P. J., Swan, K., Turk, G., Moore, M. W. & Carbone, F. R. J. exp. Med. 176, 1733–1738 (1992).
Woodland, D. L., Happ, M. P., Bill, J. & Palmer, E. Science 247, 964–967 (1990).
Gavrieli, Y., Sherman, Y. & Ben-Sasson, S. A. J. Cell Biol. 119, 493–501 (1992).
MacLennan, I. C. M. A. Rev. Immun. 12, 117–139 (1994).
Cardell, S. C. et al. Adv. Immun. 55, 423–440 (1994).
Savill, J., Fadok, V., Henson, P. & Haslett, C. Immun. Today 14, 131–136 (1993).
Veis, D. J., Sorenson, C. M., Shutter, J. R. & Korsmeyer, S. J. Cell 75, 229–240 (1993).
Duijvestijn, A. M. & Hoefsmit, E. C. M. Cell Tissue Res. 218, 279–292 (1981).
Wyllie, A. H. Nature 284, 555–556 (1980).
Anderson, R. E. & Warner, N. L. Adv. Immun. 24, 215–335 (1976).
Smith, C. A., Williams, G. T., Kingston, R., Jenkinson, E. J. & Owen, J. J. T. Nature 337, 181–184 (1989).
Shi, Y. et al. J. Immun. 146, 3340–3346 (1991).
Murphy, K. M., Heimberger, A. B. & Loh, D. Y. Science 250, 1720–1723 (1990).
Hengartner, H. et al. Nature 336, 388–390 (1988).
Pullen, A. N., Kappler, J. W. & Marrack, P. Immun. Rev. 107, 125–139 (1989).
Zijlstra, M. et al. Nature 344, 742–746 (1990).
Grusby, M. J., Johnson, R. S., Papaioannou, V. E. & Glimcher, L. H. Science 20, 1417–1420 (1991).
Surh, C. D. et al. J. exp. Med. 176, 495–505 (1992).
Malek, T. R., Robb, R. J. & Shevach, E. M. Proc. natn. Acad. Sci. U.S.A. 80, 5694–5698 (1983).
Murphy, D. B. et al. Nature 338, 765–768 (1989).
Flotte, T. J., Springer, T. A. & Thorbecke, G. J. Am. J. Path. 111, 112–124 (1983).
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Surh, C., Sprent, J. T-cell apoptosis detected in situ during positive and negative selection in the thymus. Nature 372, 100–103 (1994). https://doi.org/10.1038/372100a0
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DOI: https://doi.org/10.1038/372100a0
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