INHIBITION OF TRANSPLANT REJECTION FOLLOWING TREATMENT WITH ANTI-B7-2 AND ANTI-B7-1 ANTIBODIES
INHIBITION OF TRANSPLANT REJECTION FOLLOWING TREATMENT WITH ANTI-B7-2 AND ANTI-B7-1 ANTIBODIES
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DOI：
10.1097/00007890-199511270-00019
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发表时间：
1995-11-27
期刊：
影响因子：
6.2
通讯作者：
BLUESTONE, JA
中科院分区：
文献类型：
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作者：
LENSCHOW, DJ;ZENG, YJ;BLUESTONE, JA
抗原特异性T细胞活化最初取决于T细胞受体（TCR）与肽/MHC的相互作用。此外，由不同的细胞表面辅助分子介导的共刺激信号是导致淋巴因子产生和增殖的完全T细胞活化所必需的。CD 28被认为是T细胞上负责传递共刺激信号的主要受体，尽管已经在抗原呈递细胞（APC）上鉴定了CD 28的两种不同配体B7-1和B7-2，但是在生理免疫应答期间每种分子的共刺激作用仍然没有得到解决。在本研究中，B7-1和B7-2相互作用的相对作用进行了评估，在同种异体胰岛移植设置，在隔离，抗B7 -2单克隆抗体，并在更小的程度上，抗B7 -1单克隆抗体抑制T细胞增殖反应同种异体胰岛或脾APC在体外。使用抗B7 -1和抗B7 -2 mAb的组合观察到同种异体反应的最大抑制。施用抗B7 -2但不施用抗B7 -1 mAb延长了B6受体中的C3 H同种异体移植物存活，两种mAb的组合显著延长了排斥反应，超过单独的任一种mAb，体内mAb处理的免疫抑制作用在体外分析中没有表现出来，因为从抑制小鼠中分离的T细胞在增殖和淋巴因子产生方面对同种异体刺激反应正常，然而，联合单克隆抗体治疗在体内选择性地延迟CD 4（+）T淋巴细胞浸润到移植物。这些数据表明，B7-1和B7-2共刺激分子在体内是活跃的，虽然B7-2在这种同种异体移植模型中起着明显的主导作用。体内免疫抑制的机制尚未解决，但可能发生在与同种异体移植物不同的部位。
Antigen-specific T cell activation depends initially on the interaction of the T cell receptor (TCR) with peptide/MHC. In addition, a costimulatory signal, mediated by distinct cell surface accessory molecules, is required for complete T cell activation leading to lymphokine production and proliferation. CD28 has been implicated as the major receptor on T cells responsible for delivering the costimulatory signal, Although two distinct ligands for CD28, B7-1 and B7-2, have been identified on antigen-presenting cells (APC), the costimulatory role of each molecule during a physiological immune response remains unresolved. In the present study, the relative roles of B7-1 and B7-2 interactions were evaluated in an allogeneic pancreatic islet transplant setting, In isolation, anti-B7-2 mAbs and, to a much lesser degree, anti-B7-1 mAbs suppressed T cell proliferative responses to allogeneic islets or splenic APC in vitro. Maximal inhibition of the allogeneic response was observed using a combination of the anti-B7-1 and anti-B7-2 mAbs, Administration of anti-B7-2 but not anti-B7-1 mAbs prolonged C3H allograft survival in B6 recipients, with a combination of both mAbs significantly prolonging rejection beyond either mAb alone, The immunosuppressive effects of the in vivo mAb treatment were not manifested in in vitro analyses as T cells isolated from suppressed mice responded normally to allogeneic stimuli in terms of both proliferation and lymphokine production, However, combined mAb therapy in vivo selectively delayed CD4(+) T lymphocyte infiltration into the graft. These data suggest that both B7-1 and B7-2 costimulatory molecules are active in vivo, although B7-2 plays a clearly dominant role in this allograft model. The mechanism of immune suppression in vivo remains unresolved but may occur at sites distinct from the allograft.