4-1BB costimulatory signals preferentially induce CD8+ T cell proliferation and lead to the amplification in vivo of cytotoxic T cell responses.
4-1BB costimulatory signals preferentially induce CD8+ T cell proliferation and lead to the amplification in vivo of cytotoxic T cell responses.
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DOI：
10.1084/jem.186.1.47
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发表时间：
1997-07-07
影响因子：
15.3
通讯作者：
Mittler, RS
中科院分区：
文献类型：
--
作者：
Shuford, WW;Klussman, K;Tritchler, DD;Loo, DT;Chalupny, J;Siadak, AW;Brown, TJ;Emswiler, J;Raecho, H;Larsen, CP;Pearson, TC;Ledbetter, JA;Aruffo, A;Mittler, RS
4-1BB受体是一种可诱导的I型膜蛋白，是肿瘤坏死因子受体（TNFR）超家族的成员，在抗原或有丝分裂原诱导活化后在CD 4+和CD 8 + T细胞表面快速表达。4-1BB和活化T细胞上的T细胞受体（TCR）的交联已显示向T细胞递送共刺激信号。在这里，我们扩大了以前发表的研究表明，与CD 4 + T细胞相比，CD 8 + T细胞优先响应于早期激活事件和增殖信号提供通过TCR和4-1BB。相比之下，CD 28介导的共刺激信号似乎以与通过4-1BB共刺激诱导的信号相反的方式起作用。抗4-1BB单克隆抗体（mAb）对抗原诱导的T细胞活化的影响的体内检查表明，表位特异性抗4-1BB mAb的给药扩增了急性移植物抗宿主病（GVHD）小鼠模型中H-2d特异性细胞毒性T细胞的产生，并增强了小鼠心脏同种异体移植物或皮肤移植物排斥反应的速度。体外活化的CD 4+和CD 8 + T细胞的细胞因子分析显示，抗4-1BB共刺激显著增强CD 8 + T细胞产生干扰素-γ，并且抗4-1BB介导的CD 8 + T细胞增殖似乎不依赖于IL-2。 这些研究的结果表明，由4-1BB受体传递的调节信号在细胞毒性T细胞对抗原的细胞免疫应答的调节中起重要作用。
The 4-1BB receptor is an inducible type I membrane protein and member of the tumor necrosis factor receptor (TNFR) superfamily that is rapidly expressed on the surface of CD4+ and CD8+ T cells after antigen- or mitogen-induced activation. Cross-linking of 4-1BB and the T cell receptor (TCR) on activated T cells has been shown to deliver a costimulatory signal to T cells. Here, we expand upon previously published studies by demonstrating that CD8+ T cells when compared with CD4+ T cells are preferentially responsive to both early activation events and proliferative signals provided via the TCR and 4-1BB. In comparison, CD28-mediated costimulatory signals appear to function in a reciprocal manner to those induced through 4-1BB costimulation. In vivo examination of the effects of anti-4-1BB monoclonal antibodies (mAbs) on antigen-induced T cell activation have shown that the administration of epitope-specific anti-4-1BB mAbs amplified the generation of H-2d–specific cytotoxic T cells in a murine model of acute graft versus host disease (GVHD) and enhanced the rapidity of cardiac allograft or skin transplant rejection in mice. Cytokine analysis of in vitro activated CD4+ and CD8+ T cells revealed that anti-4-1BB costimulation markedly enhanced interferon-γ production by CD8+ T cells and that anti-4-1BB mediated proliferation of CD8+ T cells appears to be IL-2 independent. The results of these studies suggest that regulatory signals delivered by the 4-1BB receptor play an important role in the regulation of cytotoxic T cells in cellular immune responses to antigen.
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影响因子：
5.4
作者：
ALDERSON, MR;SMITH, CA;GOODWIN, RG
通讯作者：
GOODWIN, RG
影响因子：
2.2
作者：
LANE, RD
通讯作者：
LANE, RD
DOI：
10.1073/pnas.89.21.10360
发表时间：
1992-11-01
影响因子：
11.1
作者：
CHALUPNY, NJ;PEACH, R;ARUFFO, A
通讯作者：
ARUFFO, A
影响因子：
5.4
作者：
GOODWIN, RG;DIN, WS;SMITH, CA
通讯作者：
SMITH, CA
影响因子：
20.3
作者：
SCHWARZ, H;VALBRACHT, J;LOTZ, M
通讯作者：
LOTZ, M