CTLA4 and autoimmune disease: For instance, the lack of CTLA-4, PD-1, BTLA (B- and T-lymphocyte attenuator), TIGIT (T-cell immunoreceptor with immunoglobulin and ITIM domain), and VISTA (V-domain Ig suppressor of T-cell activation) was shown to cause massive lymphoproliferation, an onset of autoimmune diseases, or fatal multiorgan tissue destruction (notably CTLA-4 deficiency) (55–61).