Immune responses in 4-1BB (CD137)-deficient mice
Immune responses in 4-1BB (CD137)-deficient mice
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DOI：
10.4049/jimmunol.168.11.5483
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发表时间：
2002-06-01
影响因子：
4.4
通讯作者：
Vinay, DS
中科院分区：
文献类型：
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作者：
Kwon, BS;Hurtado, JC;Vinay, DS
4-1BB（TNFR超家族成员）是一种可诱导的共刺激分子，可独立于CD 28刺激对T细胞发挥调节作用。4-1BB（CD 137）的体外表达在用各种刺激物活化T细胞后诱导，所述刺激物包括抗TCR mAb、凝集素以及PMA和离子霉素的组合。为了进一步描述4-1BB在免疫中的生理作用，产生了该受体缺陷的小鼠。这些突变小鼠发育正常，可以存活和繁殖。对水疱性口炎病毒的体液反应与野生型小鼠相当，而突变小鼠对匙孔血蓝蛋白的IgG 2a和IgG 3同种型反应有所减少。4- 1BB缺陷型小鼠表现出增强的T细胞增殖，以响应有丝分裂原或抗CD 3，即使在环境中的能力降低，分泌生长支持细胞因子（IL-2和IL-4）。尽管来自4- 1BB缺陷小鼠的T细胞显示出增强的增殖，但是这些动物的T细胞免疫应答，例如细胞因子产生和CTL活性，被减弱。此外，4-1BB缺失似乎在髓系祖细胞生长的调节中起作用，导致外周血、骨髓和脾脏中这些前体细胞的增加。
The 4-1BB (a TNFR superfamily member) is an inducible costimulatory molecule that can exert regulatory effects on T cells independently of CD28 stimulation. The in vitro expression of 4-1BB (CD137) is induced following activation of T cells with various stimuli, including anti-TCR mAbs, lectins, and a combination of PMA and ionomycin. To delineate further the physiological role of 4-1BB in immunity, mice deficient in this receptor were generated. These mutant mice developed normally, and were viable and fertile. Humoral responses to vesicular stomatitis virus were comparable with those seen in wild-type mice, whereas the IgG2a and IgG3 isotype responses to keyhole limpet hemocyanin were somewhat reduced in the mutant mice. The 4-1BB-deficient mice demonstrated enhanced T cell proliferation in response to mitogens or anti-CD3 even in the environment of reduced ability to secrete growth-supporting cytokines (IL-2 and IL-4). Although T cells from 4-1BB-deficient mice showed enhanced proliferation, the T cell immune responses of these animals, such as cytokine production and CTL activity, were diminished. In addition, 4-1BB deletion appears to play a role in the regulation of myeloid progenitor cell growth, leading to an increase in these precursor cells in peripheral blood, bone marrow, and spleen.