T lymphocytes play a central role in regulation of the immune system. Both effector and regulatory T cells work in equilibrium to provide optimal immune response against foreign pathogens. Normally, T cells do not react against self-antigens because of the presence of central and peripheral immunogenic tolerance. Central tolerance eliminates autoreactive naive T cells that develop in thymus by presenting them with self-antigens on the thymic cells. The autoreactive T cells that escape thymus are subjected to additional mechanisms such as clonal anergy, ignorance, and deletion. Moreover, the regulatory T cells (Tregs), specifically CD4+CD25+Foxp3+ Tregs, exert a tight control over autoreactive B and T cell responses in the periphery. Failure of any one of these checkpoints can cause uncontrolled expansion of these self-reactive T cells leading to the development of autoimmune diseases. In this chapter we discuss the key role of T cells in the underlying pathogenesis of autoimmune responses. We review the role of T-cell receptor and signaling pathways including costimulatory pathways. We also review T cell inhibitory receptors such as programmed cell death protein 1 and cytotoxic T lymphocyte-associated antigen 4 and T cell-related important cytokines (interleukin [IL]-2, IL-6, IL-17, IL-7, and IL-33) involved in autoimmunity. Defects in genes responsible for T-cell regulation and function are also discussed in detail which forms the basis of many important autoimmune disorders. Various therapeutic measures that target T cells in the management of autoimmune diseases are also highlighted.
