Stimulation of human T-cell proliferation by specific activation of the 75-kDa tumor necrosis factor receptor.
Stimulation of human T-cell proliferation by specific activation of the 75-kDa tumor necrosis factor receptor.
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通过特异性激活 75-kDa 肿瘤坏死因子受体刺激人类 T 细胞增殖。
DOI：
10.4049/jimmunol.151.9.4637
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发表时间：
1993
影响因子：
4.4
通讯作者：
M. Palladino
中科院分区：
文献类型：
--
作者：
L. Tartaglia;D. Goeddel;C. Reynolds;I. Figari;Richard F. Weber;B. Fendly;M. Palladino
TNF-α可增强伴丝裂原Con A刺激的人胸腺细胞增殖。为了确定这两种不同的TNF受体是负责信号这种细胞反应，我们研究了人胸腺细胞的增殖反应的激动性抗体特异性的两种TNF受体类型。与以前研究的人细胞中的TNF活性相反，胸腺细胞增殖刺激兔多克隆抗体针对75 kDa的TNF受体（TNF-R2），但不是那些针对55 kDa的TNF受体（TNF-R1）。还显示了促红细胞生成素（TNF-β）刺激人胸腺细胞增殖，表明TNF-β可以启动由TNF-R2介导的生物反应。TNF-R2介导的T细胞增殖不限于胸腺内的未成熟T细胞，因为抗TNF-R2抗体也刺激外周T细胞的增殖。作为鉴定具有治疗潜力的TNF-R2特异性激动剂的第一步，检查了10种抗TNF-R2 mAb的潜在激动剂活性。其中9个显著刺激人胸腺细胞增殖，最大反应范围从两倍到显著大于用TNF-α本身获得的反应。
TNF-alpha can enhance the proliferation of human thymocytes stimulated by the comitogen Con A. To determine which of the two different TNF receptors is responsible for signaling this cellular response, we investigated the proliferation of human thymocytes in response to agonistic antibodies specific for the two TNF receptor types. In contrast to previously examined TNF activities in human cells, thymocyte proliferation was stimulated in response to rabbit polyclonal antibodies directed against the 75-kDa TNF receptor (TNF-R2), but not those directed against the 55-kDa TNF receptor (TNF-R1). Lymphotoxin (TNF-beta) was also shown to stimulate human thymocyte proliferation, demonstrating that TNF-beta can initiate a biologic response that is mediated by TNF-R2. TNF-R2-mediated T-cell proliferation was not restricted to the immature T cells within the thymus, as the anti-TNF-R2 antibodies also stimulated the proliferation of peripheral T cells. As a first step toward identifying a specific agonist of TNF-R2 with therapeutic potential, 10 anti-TNF-R2 mAb were examined for potential agonist activity. Nine of these significantly stimulated human thymocyte proliferation with maximal responses ranging from twofold to significantly greater than that obtained with TNF-alpha by itself.