Whereas BALB/c PD-1−/− mice develop lethal dilated cardiomyopathy, deletion of PD-1 in C57BL/6 mice results in spontaneous lupus-like autoimmune disease.81,82 T1D-prone NOD mice that are deficient for PD-1 have accelerated diabetes onset and an increased incidence of diabetes.83 Furthermore, blockade of PD-1 in EAE results in accelerated and more severe disease progression, with an increased infiltration of mononuclear cells into the CNS.84 Polymorphisms in the PD-1 locus in humans have been associated with SLE, T1D, ankylosing spondylitis, and rheumatoid arthritis.85–88. This evidence concerns the gene PDCD1 and rheumatoid arthritis.