Allison J P, Chambers C, Hurwitz A, Sullivan T, Boitel B, Fournier S, Brunner M, Krummel M
Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720-3200, USA.
Novartis Found Symp. 1998;215:92-8; discussion 98-102, 186-90. doi: 10.1002/9780470515525.ch7.
Occupancy of the antigen receptor is not sufficient for activation of naïve T cells--additional co-stimulatory signals are required that can be provided only by 'professional' antigen-presenting cells. This two-signal model for T cell activation has been thought to provide a mechanism for the induction and maintenance of peripheral tolerance. Work over the past six years has demonstrated that the relevant co-stimulatory receptor on T cells is the molecule CD28. Recent data shows that the CD28 homologue CTLA-4 plays a role in negative regulation of T cell responses. Here we suggest that CTLA-4 may also serve as an attenuator of T cell-activating signals, raising the threshold of stimulation required to obtain full activation. The inhibitory signals mediated by CTLA-4 may provide an additional mechanism for the maintenance of peripheral tolerance.
抗原受体的占据不足以激活初始T细胞——还需要额外的共刺激信号，而这些信号只能由“专职”抗原呈递细胞提供。T细胞激活的这种双信号模型被认为提供了一种诱导和维持外周耐受的机制。过去六年的研究表明，T细胞上相关的共刺激受体是分子CD28。最近的数据显示，CD28同源物CTLA-4在T细胞反应的负调节中发挥作用。在此我们提出，CTLA-4也可能作为T细胞激活信号的衰减器，提高获得完全激活所需的刺激阈值。由CTLA-4介导的抑制性信号可能为维持外周耐受提供一种额外机制。
