Abstract
ACTIVATED T lymphocytes proliferate in response to interIeukin-2 (IL-2), which binds to a specific high-affinity receptor (IL -2R)1–3 This consists of at least two noncovalently linked polypeptides, p55/IL-2Rα (Tac)4 and p75/IL-2Rβ5–7. Both molecules bind IL-2 independently, with low and intermediate affinity respectively5–10, but only IL-2Rβ3 is thought to mediate IL-2 signal transduction8,11–13. Although IL-2Rβ seems to be constitutively expressed on resting T lymphocytes9,14, the growth of these T cells is specifically induced by antigenic triggering by the T-cell receptor (TCR), which then results in the transcription of both IL-2 and IL-2Rα genes1,2,15. By contrast, activation of the IL-2/IL-2R pathway in the thymus seems to precede the appearance of the TCR, as IL-2Rα is expressed on T-cell precursors lacking TCR16–21. The basis for IL-2R expression by immature thymocytes, however, remains largely unknown. We show here that IL-2Rα-negative T-cell precursors constitutively express IL-2Rβ and produce their own IL-2. The IL-2/IL-2Rβ interaction on these cells induces the expression of IL-2Rα, leading to high-affinity IL-2R display and cellular proliferation. We suggest that this IL-2-dependent autocrine pathway of growth stimulation plays a key role in the intrathymic development of mature T cells.
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References
Smith, K. A. Immunol. Rev. 51, 335–357 (1980).
Robb, R. J., Munck, A. & Smith, K. A. J. exp. Med. 154, 1455–1474 (1981).
Robb, R. J., Greene, W. C. & Rusk, C. M. J. exp. Med. 160, 1126–1146 (1984).
Leonard, W. J. et al. Nature 300, 267–269 (1982).
Sharon, M., Klausner, R. D., Cullen, B. R., Chizzonite, R. & Leonard, W. J. Science 234, 859–863 (1986).
Tsudo, M., Kozak, R. W., Goldman, C. K. & Waldmann, T. A. Proc. natn. Acad. Sci. U.S.A. 83, 9694–9698 (1986).
Teshigawara, K., Wang, H., Kato, K. & Smith, K. A. J. exp. Med. 165, 223–238 (1986).
Wang, H. M. & Smith, K. A. J. exp. Med. 166, 1055–1069 (1987).
Dukovich, M. et al. Nature 327, 518–522 (1987).
Robb, R. J., Rusk, C. M., Yodoi, J. & Greene, W. C. Proc. natn. Acad. Sci. U.S.A. 84, 2002–2006 (1987).
Robb, R. J. & Greene, W. C. J. exp. Med. 165, 1201–1206 (1987).
Smith, K. A. Immun. Today 9, 36–37 (1988).
Tanaka, T., Saiki, O., Doi, S., Negoro, S. & Kishimoto, S. J. Immun. 140, 470–473 (1988).
Bich-Thuy, L. T. et al. J. Immun. 139, 1550–1556 (1987).
Meuer, S. C. et al. Proc. natn. Acad. Sci. U.S.A. 81, 1509–1513 (1984).
Raulet, D. H. Nature 314, 101–103 (1985).
Ceredig, R., Lowenthal, J. W., Nabholz, M. & MacDonald, H. R. Nature 314, 98–100 (1985).
de la Hera, A. et al. Eur. J. Immun. 16, 653–658 (1986).
Shimonkevitz, R. P., Husmann, L. A., Bevan, M. J. & Crispe, I. N. Nature 329, 157–159 (1987).
Jenkinson, E. J., Kingston, R. & Owen, J. J. T. Nature 329, 160–162 (1987).
Toribio, M. L. et al. Immunol. Rev. 104, 55–79 (1988).
Toribio, M. L. et al. J. exp. Med. 168, 2231–2249 (1988).
de la Hera, A., Toribio, M. L., Marcos, M. A. R., Márquez, C. & Martínez-A., C. Eur. J. Immun. 17, 683–687 (1987).
Carding, S. R. et al. Proc. natn. Acad. Sci. U.S.A. 86, 3342–3345 (1989).
de la Hera, A., Toribio, M. L. & Martínez-A., C. International Immun. (in the press).
Carrera, A. C., Sánchez-Madrid, F., López-Botet, M., Bernabeu, C. & O. de Landázuri, M. Eur. J. Immun. 17, 179–186 (1987).
Munson, P. J. & Rodbard, D. Analyt. Biochem. 107, 220–239 (1980).
Nikaido, T. et al. Nature 331, 631–635 (1984).
Taniguchi, T. et al. Nature 302, 305–310 (1983).
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Toribio, M., Gutiérrez-Ramos, J., Pezzi, L. et al. lnterleukin-2-dependent autocrine proliferation in T-cell development. Nature 342, 82–85 (1989). https://doi.org/10.1038/342082a0
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DOI: https://doi.org/10.1038/342082a0
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