The regulation of PD-1/PD-L1 pathway and autoimmune diseases

PD-1 is an immuno-inhibitory receptor which belongs to the immunoglobulin superfamily and expressed on activated T, B and myeloid cells. Engagement of the PD-1 receptor with its membrane bound ligand (PD-LI) of the B7 family inhibits the proliferation of anti-CD3 stimulated T cells as well as anti-IgM stimulated B cells (Freeman et al. 2000 and our unpublished observation). Disruption of PD-1 gene in C57BL/6 mice caused typical lupus-like glomerulonephritis and destructive arthritis as they age (Nishimura et al. 1999) while in BALB/c mice caused autoantibody mediated dilated cardiomyopathy with severely impaired contraction and sudden death by congestive heart failure. Affected hearts showed diffuse deposition of IgG on the surface of cardiomyocytes. All of the affected PD-1(-/-) mice exhibited high-titered circulating IgG autoantibodies reactive to a 33-kDa protein expressed specifically on the surface of cardiomyocytes (Nishimura et al. 2001). These results indicate that PD-1 may be an important factor contributing to the prevention of autoimmune diseases.