Unlike CD28, CTLA-4 dampens T-cell responses in a manner that can protect against the development of auto-proliferative or autoimmune disease [2, 17, 18, 19] CTLA-4-deficient (Ctla-4−/−) mice show a profound hyper-proliferative phenotype leading to death within 3 weeks of age due to massive tissue infiltration and organ destruction [6]. Here, CTLA4 is linked to autoimmune disease.