Additionally, studies using gain-of-function and loss-of-function mouse models, as well as specific human patient populations, have demonstrated that ICPs and their ligands, including PD-1/PD-L1, CTLA-4/CD80 and CD86, ICOSL (CD275)/ICOS (CD278), CD40/CD40L (CD154), OX40 (CD134)/OX40L (CD252), GITR (TNFRSF18)/GITRL (TNFSF18)/ and TIM (HAVCR2, CD366) axes, are associated with an increased risk of vein graft disease [35], graft arterial disease [36], atherosclerosis [37–40], coronary heart disease, ischemic stroke [25,26], myocarditis [41], cardiomyopathy [42], and heart failure [43]. This evidence concerns the gene TNFRSF4 and ischemic stroke.