Bamford R N, Grant A J, Burton J D, Peters C, Kurys G, Goldman C K, Brennan J, Roessler E, Waldmann T A
Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1994 May 24;91(11):4940-4. doi: 10.1073/pnas.91.11.4940.
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 subunit. 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 IL-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-IL-2R 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.
晚期人类嗜T细胞病毒I相关的成人T细胞白血病细胞表达白细胞介素2受体（IL-2R），但不再产生白细胞介素2。我们曾报道，不依赖白细胞介素2的成人T细胞白血病细胞系HuT-1分泌一种细胞因子，暂命名为IL-T，它能刺激T细胞增殖和淋巴因子激活的杀伤细胞活性。由HuT-102条件培养基或3200倍纯化的IL-T介导的对细胞因子依赖的人类T细胞系Kit-225增殖的刺激，不会因添加抗白细胞介素2或IL-2Rα亚基的抗体而被阻断。然而，添加特异性结合IL-2Rβ亚基的抗体Mik-β1可抑制IL-T对该人类T细胞系的刺激。此外，由含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，不会因针对白细胞介素2或IL-2α的抗体而被阻断，但会被抗IL-2Rβ抗体抑制，这表明该受体亚基是IL-T发挥作用所必需的。使用表达IL-2Rα和IL-2Rγ但不表达IL-2Rβ的IL-3依赖的小鼠髓系前体细胞系32D证实了这一结论。白细胞介素2和IL-T均未刺激32D细胞增殖。然而，在用编码人类IL-2Rβ的基因转染后，添加任何一种细胞因子时32Dβ细胞都会增殖。抗IL-2Rβ抗体可抑制IL-T介导的32Dβ增殖刺激，但抗白细胞介素2抗体则无此作用。因此，IL-T介导的T细胞刺激和淋巴因子激活的杀伤细胞激活需要IL-2Rβ亚基的表达。
