INTERLEUKIN-2-DEPENDENT AUTOCRINE PROLIFERATION IN T-CELL DEVELOPMENT
INTERLEUKIN-2-DEPENDENT AUTOCRINE PROLIFERATION IN T-CELL DEVELOPMENT
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DOI：
10.1038/342082a0
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发表时间：
1989-11-02
期刊：
影响因子：
64.8
通讯作者：
MARTINEZ, C
中科院分区：
文献类型：
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作者：
TORIBIO, ML;GUTIERREZRAMOS, JC;MARTINEZ, C
活化的T淋巴细胞响应白细胞介素-2（IL-2）而增殖，白细胞介素-2与特异性高亲和力受体（IL-2 R β 1 - 3）结合。该受体由至少两个非共价连接的多肽p55/IL-2 R α（Tac）4和p75/IL-2 R β5-7组成。两种分子分别以低亲和力和中等亲和力独立结合IL-2 5 -10，但认为仅IL-2 R β3介导IL-2信号转导8，11-13。尽管IL-2 R β似乎在静息T淋巴细胞上组成型表达9，14，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，然后导致IL-2和IL-2 R α基因的转录1，2，15。相比之下，胸腺中IL-2/IL-2 R途径的激活似乎先于TCR的出现，因为IL-2 R α在缺乏TCR 16 -21的T细胞前体上表达。然而，未成熟胸腺细胞表达IL-2 R的基础在很大程度上仍然未知。我们在此发现，IL-2 R α阴性T细胞前体组成性表达IL-2 R β并产生其自身的IL-2。这些细胞上的IL-2/IL-2 R β相互作用诱导IL-2 R α表达，导致高亲和力IL-2 R展示和细胞增殖。我们认为，这种IL-2依赖的自分泌途径的生长刺激中起着关键作用，在胸腺内发育的成熟T细胞。
ACTIVATED T lymphocytes proliferate in response to interIeukin-2 (IL-2), which binds to a specific high-affinity receptor (IL -2R)1–3This consists of at least two noncovalently linked polypeptides, p55/IL-2Rα (Tac)4and 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.