Samoilova E B, Horton J L, Zhang H, Khoury S J, Weiner H L, Chen Y
Institute for Human Gene Therapy and Department of Molecular and Cellular Engineering, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Int Immunol. 1998 Apr;10(4):491-8. doi: 10.1093/intimm/10.4.491.
Mucosal and systemic administrations of high dose antigens induce long-lasting peripheral T cell tolerance. We and others have shown that high dose peripheral T cell tolerance is mediated by anergy or deletion and is preceded by T cell activation. Co-stimulatory molecules B7-1 (CD80)/B7-2 (CD86) and their counter-receptors CD28/CTLA-4 play pivotal roles in T cell activation and immune regulation. In the present study, we examined the roles of the B7 co-stimulation pathway in the generation of high dose peripheral T cell tolerance. We found that blocking B7:CD28/CTLA-4 interaction at the time of tolerance induction partially prevented T cell tolerance, whereas selective blockade of B7:CTLA-4 interaction completely abrogated peripheral T cell tolerance induced by either oral or i.p. antigens. These results suggest that CTLA-4-mediated feedback regulation plays a crucial role in the induction of high dose peripheral T cell tolerance.
高剂量抗原的黏膜和全身给药可诱导持久的外周T细胞耐受。我们及其他研究人员已表明，高剂量外周T细胞耐受由无反应性或细胞凋亡介导，且在T细胞活化之前发生。共刺激分子B7-1（CD80）/B7-2（CD86）及其反受体CD28/CTLA-4在T细胞活化和免疫调节中起关键作用。在本研究中，我们研究了B7共刺激途径在高剂量外周T细胞耐受产生中的作用。我们发现，在耐受诱导时阻断B7:CD28/CTLA-4相互作用可部分阻止T细胞耐受，而选择性阻断B7:CTLA-4相互作用则完全消除了口服或腹腔注射抗原诱导的外周T细胞耐受。这些结果表明，CTLA-4介导的反馈调节在高剂量外周T细胞耐受的诱导中起关键作用。
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