THE INTERLEUKIN (IL)-2 RECEPTOR-BETA CHAIN IS SHARED BY IL-2 AND A CYTOKINE, PROVISIONALLY DESIGNATED IL-T, THAT STIMULATES T-CELL PROLIFERATION AND THE INDUCTION OF LYMPHOKINE-ACTIVATED KILLER-CELLS
THE INTERLEUKIN (IL)-2 RECEPTOR-BETA CHAIN IS SHARED BY IL-2 AND A CYTOKINE, PROVISIONALLY DESIGNATED IL-T, THAT STIMULATES T-CELL PROLIFERATION AND THE INDUCTION OF LYMPHOKINE-ACTIVATED KILLER-CELLS
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DOI：
10.1073/pnas.91.11.4940
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发表时间：
1994-05-24
影响因子：
11.1
通讯作者：
WALDMANN, TA
中科院分区：
文献类型：
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作者：
BAMFORD, RN;GRANT, AJ;WALDMANN, TA
晚期人 T 细胞嗜淋巴细胞病毒 I 相关的成人 T 细胞白血病细胞表达 IL-2 受体 (IL-2R)，但不再产生 IL-2。我们报道了不依赖 IL-2 的成人 T 细胞白血病系 HuT-102 分泌一种细胞因子，暂时命名为 IL-T，可刺激 T 细胞增殖和淋巴因子激活的杀伤细胞活性。 HuT-102条件培养基或3200倍纯化的IL-T介导的细胞因子依赖性人T细胞系Kit-225的增殖刺激不会因添加抗IL-2或IL-2Rα抗体而被阻断。然而，IL-T 介导的对该人类 T 细胞系的刺激可通过添加 Mik-beta-1（一种与 IL-2R β 亚基特异性结合的抗体）来抑制。此外，由含有 IL-T 的条件培养基介导的大颗粒淋巴细胞向淋巴因子激活的杀伤细胞的激活不会被针对 IL-2 或 IL-2 α 的抗体阻断，但会被针对 IL-2R β 的抗体抑制，这表明该受体亚基对 IL-T 作用是必需的。这一结论得到了 IL-3 依赖性小鼠骨髓前体细胞系 32D 的证实，该细胞表达 H-2R α 和 IL-2R γ，但不表达 IL-2R β。IL-2 和 IL-T 均不刺激 32D 细胞增殖。然而，在用编码人IL-2Rβ的基因转染后，32Dβ细胞在添加任一细胞因子时增殖。 IL-T介导的32Dβ增殖刺激被抗IL2Rβ抗体抑制，但不被抗IL-2抗体抑制。因此，IL-T 介导的 T 细胞刺激和淋巴因子激活的杀伤细胞活化需要 IL-2R β 亚基的表达。
Late-phase human T-cell lymphotropic virus I-associated adult T-cell leukemia cells express IL-2 receptors (IL-2R) but no longer produce IL-2. We have reported that the IL-2-independent adult T-cell leukemia line HuT-102 secretes a cytokine, provisionally designated IL-T, that stimulates T-cell proliferation and lymphokine-activated killer cell activity. Stimulation of proliferation of the cytokine-dependent human T-cell line Kit-225 mediated by HuT-102 conditioned medium or by 3200-fold purified IL-T was not blocked by the addition of antibodies against IL-2 or IL-2R alpha submit. However, IL-T-mediated stimulation of this human T-cell line was inhibited by addition of Mik-beta-1, an antibody that binds specifically to IL-2R beta subunit. In addition, the activation of large granular lymphocytes to lymphokine-activated killer cells mediated by IL-T-containing conditioned medium was not blocked by antibodies directed toward IL-2 or IL-2 alpha but was inhibited by an antibody to IL-2R beta, suggesting the requirement of this receptor subunit for IL-T action. This conclusion was confirmed using an IL-3-dependent murine myeloid precursor cell line, 32D, that expresses H-2R alpha and IL-2R gamma, but not IL-2R beta Neither IL-2 nor IL-T stimulated 32D cell proliferation. However, after transfection with the gene encoding human IL-2R beta, 32D beta cells proliferated on addition of either cytokine. The IL-T-mediated stimulation of 32D beta proliferation was inhibited by an anti-IL2R beta antibody but not by an anti-IL-2 antibody. Thus, the IL-T-mediated stimulation of T-cell and lymphokine-activated killer cell activation requires the expression of the IL-2R beta subunit.