Molecular mechanisms of T-cell tolerance

CD4(+) T cells are the master regulators of adaptive immune responses, and many autoimmune diseases arise due to a breakdown of self-tolerance in CD4(+) T cells. Activation of CD4(+) T cells is regulated by not only the binding of peptide-major histocompatibility complexes to T-cell receptor but also costimulatory signals from antigen-presenting cells. Recently, there has been progress in understanding the extracellular and intracellular mechanisms that are required for implementation and maintenance of T-cell tolerance. Understanding of the molecular mechanisms underlying T-cell tolerance will lead to development of pharmacological approaches either to promote the tolerance state in terms of autoimmunity or to break tolerance in cancer.