PD-L1, a Type I Interferon-regulated Immune Checkpoint Protein in Sepsis

Author(s): Professor. Yusen Liu, Evan Shelton

Programmed death-ligand 1 (PD-L1) is one of the best understood immune checkpoint proteins^1,2. PD-L1 can inhibit the clonal expansion of CD8+ and CD4+ T lymphocytes through engaging with another inhibitory immune checkpoint molecule programmer death (PD)-1 expressed on T lymphocytes. In response to exogenous or endogenous danger signals, the adaptive immune system reacts to foreign antigens with rapid clonal expansion of antigen-specific CD8+ cytotoxic or CD4+ helper T lymphocytes. Engagement of PD-L1 with PD-1 leads to recruitment of tyrosine phosphatases SHP-2 via immunoreceptor tyrosine switch motif of PD-1, resulting in inhibition of the proliferation of antigen-specific T cells in lymph nodes and reduction of apoptosis of regulatory T cells³. It has been speculated that PD-L1 plays an important role in suppressing the adaptive immune system during pregnancy⁴, tissue allografts ^5,6, and autoimmune disease^7-9

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