CTLA-4, also known as CD152, is a transmembrane protein expressed in activated CD4+ and CD8+ T cells.134,135–138 While CD28 was found to be a T-cell costimulatory molecule,139 CTLA-4 was later discovered to mimic CD28 and act as a brake on T-cell activation.140,141 Under physiological conditions, CTLA-4 and CD80/CD86 binding can inhibit T-cell activation signals and prevent autoimmune disease.142,143 Blocking CTLA-4 can directly target inhibitory signals on effector T cells and reduce the inhibitory effect of Tregs,33,144–147 thus effectively enhancing the antitumor effect of T cells. The gene discussed is CD28; the disease is autoimmune disease.