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首页> 美国卫生研究院文献>The Journal of Experimental Medicine >Anti–4-1bb Monoclonal Antibodies Abrogate T Cell–Dependent Humoral Immune Responses in Vivo through the Induction of Helper T Cell Anergy
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Anti–4-1bb Monoclonal Antibodies Abrogate T Cell–Dependent Humoral Immune Responses in Vivo through the Induction of Helper T Cell Anergy

机译：抗4-1bb单克隆抗体通过诱导辅助性T细胞无能消除了体内依赖T细胞的体液免疫反应。

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The 4-1BB receptor (CDw137), a member of the tumor necrosis factor receptor superfamily, has been shown to costimulate the activation of T cells. Here we show that anti–mouse 4-1BB monoclonal antibodies (mAbs) inhibit thymus-dependent antibody production by B cells. Injection of anti–4-1BB mAbs into mice being immunized with cellular or soluble protein antigens induced long-term anergy of antigen-specific T cells. The immune response to the type II T cell–independent antigen trinintrophenol-conjugated Ficoll, however, was not suppressed. Inhibition of humoral immunity occurred only when anti–4-1BB mAb was given within 1 wk after immunization. Anti–4-1BB inhibition was observed in mice lacking functional CD8+ T cells, indicating that CD8+ T cells were not required for the induction of anergy. Analysis of the requirements for the anti–4-1BB–mediated inhibition of humoral immunity revealed that suppression could not be adoptively transferred with T cells from anti–4-1BB–treated mice. Transfer of BALB/c splenic T cells from sheep red blood cell (SRBC)-immunized and anti–4-1BB–treated mice together with normal BALB/c B cells into C.B-17 severe combined immunodeficient mice failed to generate an anti-SRBC response. However, B cells from the SRBC-immunized, anti–4-1BB–treated BALB/c mice, together with normal naive T cells, exhibited a normal humoral immune response against SRBC after transfer, demonstrating that SRBC-specific B cells were left unaffected by anti–4-1BB mAbs.
机译：4-1BB受体（CDw137）是肿瘤坏死因子受体超家族的成员，已被证明可以共同刺激T细胞的活化。在这里，我们显示抗小鼠4-1BB单克隆抗体（mAbs）抑制B细胞产生的胸腺依赖性抗体。向用细胞或可溶性蛋白抗原免疫的小鼠中注射抗4-1BB mAb会引起抗原特异性T细胞的长期无反应。然而，对II型T细胞非依赖性抗原三硝基酚结合的Ficoll的免疫反应并未受到抑制。仅在免疫后1周内给予抗4-1BB mAb才抑制体液免疫。在缺乏功能性CD8 + T细胞的小鼠中观察到抗4-1BB抑制作用，表明CD8 + T细胞不是诱导无反应性所必需的。对抗4-1BB介导的体液免疫抑制要求的分析表明，抑制不能通过抗4-1BB处理的小鼠的T细胞过继转移。从绵羊红细胞（SRBC）免疫和抗4-1BB处理的小鼠中，将BALB / c脾脏T细胞与正常BALB / c B细胞一起转移至CB-17严重联合免疫缺陷小鼠中，但未能产生抗SRBC响应。但是，经SRBC免疫，抗4-1BB处理的BALB / c小鼠的B细胞，与正常的T细胞一起，在转移后对SRBC表现出正常的体液免疫反应，表明SRBC特异的B细胞不受影响。抗4-1BB单克隆抗体。

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