Journal of Clinical and Cellular Immunology
Open Access

Abstract

The Role of T-Cell Costimulatory Pathways in Regulation of Autoimmune Diabetes

I-Fang Lee, Dawei Ou, Daniel L. Metzger and Garth L. Warnock

Many factors contribute to the pathogenesis of autoimmune diabetes. Targets for treating this debilitating disease will become more apparent by understanding the nature of immune activation. This review examines the possibility of targeting costimulation and discusses the molecules found on the T cell and the antigen-presenting cell (APC) that participate in T-cell activation. The B7-1/B7-2:CD28/cytotoxic T lymphocyte antigen-4 (CTLA-4) pathway has been shown to be crucial in regulating T-cell activation and tolerance. Novel members of the B7-CD28 superfamily have recently been discovered, and they appear to be particularly important for regulating the responses of previously activated T cells. Superimposition of inhibitory signals, such as those delivered by CTLA-4 and the programmed death (PD)-1-PD-1 ligand (PD-L1) pathway, leads to a complex network of positive and negative costimulatory signals, the integration of which modulates immune responses. Furthermore, expression of the B7 homolog B7-H4 on cells in peripheral tissues indicates new mechanisms for regulating T-cell responses. This review focuses on our current understanding of the members of the B7:CD28 superfamily and discusses their therapeutic potential in autoimmune diabetes.