Abstract
The binding of programmed death 1 (PD-1) to its ligands PD-L1 and PD-L2 on antigen-presenting cells has been proven to turn off autoreactive T cells and induce peripheral tolerance. In this study, fusion proteins linking the extracellular domains of murine PD-1, PD-L1 and PD-L2 to the Fc portion of a mouse immunoglobulin G2a monoclonal antibody were generated and characterized. Onset of proteinuria was delayed with mice treated with PD-LIg fusion proteins, while serum concentrations of anti-dsDNA and anti-histone antibodies were reduced by the treatment of PD-LIg without decreasing total IgG with significantly improved survival. Importantly, PD-L1Ig treatment was the most efficacious in delaying the onset of proteinuria, blocking auto-antibody production, and prolonging life time, including a delayed treatment until disease progression. These findings indicate that human PD-L1Ig fusion proteins may play an important role in conquering humans' autoimmune diseases.
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