CD152/CTLA-4 (Cytotoxic T-lymphocyte protein 4, Cytotoxic T-lymphocyte-associated antigen 4, CD152 antigen, Cytotoxic T lymphocyte antigen 4)

Cytotoxic T lymphocyte associated gene –4 (CTLA-4) was initially described as a classical type I glycoprotein on the surface of activated T-cells (1). CTLA-4 is a member of the Ig gene superfamily and along with its homologue, CD28, is a B7 binding protein. There is evidence that CTLA-4 is a negative regulator of T-cell activation, ligation of CTLA-4 on the T-cell surface initiates a series of biochemical events that attenuate an ongoing immune response . CTLA-4 knock out mice demonstrate profound polyclonal lymphoproliferative disoders that infiltrate most major organ systems and the animals die a few weeks after birth. The animals have increased levels of IgG which illustrates the role of CTLA-4 on humoral immune responses as well. A role for CTLA-4 in autoimmune disease is suggested by the observations that blockade of B7/CTLA-4 interaction exacerbates animal models of autoimmune disease such as experimental autoimmune encephalomyelitis and diabetes. A search for genetic markers that segregate with Graves‘ disease revealed an association with CTLA-4 polymorphisms. CTLA-4 is further more closely linked to autoimmune thyroid disease (ATD). A native soluble form of CTLA-4 has been described to be present in human serum . A correlation of circulating CTLA-4 and ATD has been shown.