Toribio M L, Gutiérrez-Ramos J C, Pezzi L, Marcos M A, Martínez C
Centro de Biología Molecular (CSIC), Universidad Autónoma de Madrid, Spain.
Nature. 1989 Nov 2;342(6245):82-5. doi: 10.1038/342082a0.
Activated T lymphocytes proliferate in response to interleukin-2 (IL-2), which binds to a specific high-affinity receptor (IL-2R). This consists of at least two noncovalently linked polypeptides, p55/IL-2R alpha (Tac) and p75/IL-2R beta. Both molecules bind IL-2 independently, with low and intermediate affinity respectively, but only IL-2R beta is thought to mediate IL-2 signal transduction. Although IL-2R beta seems to be constitutively expressed on resting T lymphocytes, 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-2R alpha genes. By contrast, activation of the IL-2/IL-2R pathway in the thymus seems to precede the appearance of the TCR, as IL-2R alpha is expressed on T-cell precursors lacking TCR. The basis for IL-2R expression by immature thymocytes, however, remains largely unknown. We show here that IL-2R alpha-negative T-cell precursors constitutively express IL-2R beta and produce their own IL-2. The IL-2/IL-2R beta interaction on these cells induces the expression of IL-2R alpha, 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.
活化的T淋巴细胞会对白介素-2（IL-2）产生增殖反应，IL-2可与一种特定的高亲和力受体（IL-2R）结合。该受体至少由两种非共价连接的多肽组成，即p55/IL-2Rα（Tac）和p75/IL-2Rβ。这两种分子均可独立结合IL-2，亲和力分别较低和中等，但只有IL-2Rβ被认为可介导IL-2信号转导。尽管IL-2Rβ似乎在静止的T淋巴细胞上组成性表达，但这些T细胞的生长是由T细胞受体（TCR）的抗原触发特异性诱导的，随后会导致IL-2和IL-2Rα基因的转录。相比之下，胸腺中IL-2/IL-2R途径的激活似乎先于TCR的出现，因为IL-2Rα在缺乏TCR的T细胞前体上表达。然而，未成熟胸腺细胞表达IL-2R的基础在很大程度上仍然未知。我们在此表明，IL-2Rα阴性的T细胞前体组成性表达IL-2Rβ并产生自身的IL-2。这些细胞上的IL-2/IL-2Rβ相互作用会诱导IL-2Rα的表达，导致高亲和力IL-2R的展示和细胞增殖。我们认为，这种依赖IL-2的自分泌生长刺激途径在成熟T细胞的胸腺内发育中起关键作用。
