Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a member of the CD28 superfamily and is a negative regulator of T cell-mediated immune responses. CTLA-4 expression is induced on the surface of T cells after CD28 binding and activation, and is constitutively expressed on T-regulatory cells, acting as an immune checkpoint inhibitor, downregulating T cell activity. CTLA-4 primarily inactivates T-cell activity by competing with the CD28 costimulatory molecule. CD28 and CTLA-4 share the identical ligands of CD80 and CD86 on antigenpresenting cells; and thus CTLA-4 competes with CD28 function in T-cell survival, proliferation, and recruitment. In particular, CTLA-4 down-modulates CD4+ helper T-cell activity and enhances Treg immunosuppressive functions. CTLA-4 has been shown to play a role in human diseases. CTLA-4 acts as a physiological brake on the activated immune system in order to maintain immune homeostasis. Several suppressive mechanisms for T-cell functions have been attributed to CTLA-4.
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