Superantigen responses and co-stimulation: CD28 and CTLA-4 have opposing effects on T cell expansion in vitro and in vivo
Superantigen responses and co-stimulation: CD28 and CTLA-4 have opposing effects on T cell expansion in vitro and in vivo
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DOI：
10.1093/intimm/8.4.519
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发表时间：
1996-04-01
影响因子：
4.4
通讯作者：
Allison, JP
中科院分区：
文献类型：
--
作者：
Krummel, MF;Sullivan, TJ;Allison, JP
通过CD 28/CTLA-4系统的共刺激对于T细胞增殖至与MHC相关的肽抗原似乎是关键的。本研究探讨了CD 28和CTLA-4在小鼠T细胞对超抗原葡萄球菌肠毒素B（SE B）应答中的作用。体外实验表明，抗B7-1/B7-2抗体或抗CD 28抗体的Fab B片段可显著抑制脾细胞对SE B的应答。相反，抗CTLA-4抗体的Fab片段增强了增殖反应。此外，针对B7-1/B7-2的阻断抗体的添加增加了由完整抗CD 28抗体共刺激的增殖。这些数据支持CD 28和CTLA-4对早期T细胞活化发挥相反作用的假设。在体内，完整的抗CD 28抗体和抗CD 28的非刺激性Fab片段似乎对V（β）8（+）T细胞的扩增具有相似的抑制作用。相反，完整的抗CTLA-4抗体和抗CTLA-4的Fab片段似乎都放大了这种扩增。我们得出结论，SEB应答被CD 28衍生的信号传导显著增强，这反过来又可能被通过CTLA-4的信号减弱。
Co-stimulation via the CD28/CTLA-4 system appears critical for T cell proliferation to peptide antigens presented in association with MHC. In this study, we examine the roles of CD28 and CTLA-4 in the response of murine T cells to the superantigen staphylococcal enterotoxin B (SEB), In vitro, antibodies against B7-1/B7-2 or Fab fragments of anti-CD28 antibodies significantly inhibit the response of splenocytes to SEB. Conversely, Fab fragments of anti-CTLA-4 antibodies augment the proliferative response. Further, addition of blocking antibodies directed against B7-1/B7-2 augment proliferation co-stimulated by intact anti-CD28 antibodies, These data support the hypothesis that CD28 and CTLA-4 exert opposing effects upon early T cell activation. In vivo, intact anti-CD28 antibodies and non-stimulatory Fab fragments of anti-CD28 appear to have similar inhibitory effects upon the expansion of V(beta)8(+) T cells, In contrast, both intact and Fab fragments of anti-CTLA-4 appear to amplify this expansion, We conclude that the SEB response is significantly augmented by CD28-derived signaling and this in turn may be attenuated by signals through CTLA-4.