lnterleukin-2-dependent autocrine proliferation in T-cell development

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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.