Chambers C A, Kuhns M S, Egen J G, Allison J P
University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Annu Rev Immunol. 2001;19:565-94. doi: 10.1146/annurev.immunol.19.1.565.
The T cell compartment of adaptive immunity provides vertebrates with the potential to survey for and respond specifically to an incredible diversity of antigens. The T cell repertoire must be carefully regulated to prevent unwanted responses to self. In the periphery, one important level of regulation is the action of costimulatory signals in concert with T cell antigen-receptor (TCR) signals to promote full T cell activation. The past few years have revealed that costimulation is quite complex, involving an integration of activating signals and inhibitory signals from CD28 and CTLA-4 molecules, respectively, with TCR signals to determine the outcome of a T cell's encounter with antigen. Newly emerging data suggest that inhibitory signals mediated by CTLA-4 not only can determine whether T cells become activated, but also can play a role in regulating the clonal representation in a polyclonal response. This review primarily focuses on the cellular and molecular mechanisms of regulation by CTLA-4 and its manipulation as a strategy for tumor immunotherapy.
适应性免疫中的T细胞区室使脊椎动物有潜力去探测并特异性地应对种类繁多的抗原。T细胞库必须得到精心调控，以防止对自身产生不必要的反应。在外周，一个重要的调控层面是共刺激信号与T细胞抗原受体（TCR）信号协同作用，以促进T细胞的完全活化。过去几年的研究表明，共刺激相当复杂，分别涉及来自CD28和CTLA-4分子的激活信号和抑制信号与TCR信号的整合，以决定T细胞与抗原相遇的结果。新出现的数据表明，CTLA-4介导的抑制信号不仅能决定T细胞是否被激活，还能在多克隆反应中调节克隆代表性方面发挥作用。本综述主要关注CTLA-4的调控细胞和分子机制及其作为肿瘤免疫治疗策略的操控。
