In contrast to CTLA-4 −/− mice in which most of the CD4+ T cells are non-specifically activated and invade various organs, knockout mice for PD-1 showed autoimmune alteration, including lupus-like proliferative arthritis and myocarditis with high-titter auto-antibodies against cardiac myosin, which indicates that these alterations could be mediated by an antigen-specific autoimmune response [17,18]. The gene discussed is CTLA4; the disease is myocarditis.