PD-L1 has distinct functions in hematopoietic and nonhematopoietic cells in regulating T cell responses during chronic infection in mice.
Mueller, Scott N. 1; Vanguri, Vijay K. 2; Ha, Sang-Jun 1; West, Erin E. 1; Keir, Mary E. 2; Glickman, Jonathan N. 2; Sharpe, Arlene H. 2; Ahmed, Rafi 1
[Article]
Journal of Clinical Investigation.
120(7):2508-2515, July 1, 2010.
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The inhibitory receptor programmed death 1 (PD-1) is upregulated on antigen-specific CD8 T cells during persistent viral infections. Interaction with PD-1 ligand 1 (PD-L1) contributes to functional exhaustion of responding T cells and may limit immunopathology during infection. PD-L1 is expressed on both hematopoietic and nonhematopoietic cells in tissues. However, the exact roles of PD-L1 on hematopoietic versus nonhematopoietic cells in modulating immune responses are unclear. Here we used bone marrow chimeric mice to examine the effects of PD-L1 deficiency in hematopoietic or nonhematopoietic cells during lymphocytic choriomeningitis virus clone 13 (LCMV CL-13) infection. We found that PD-L1 expression on hematopoietic cells inhibited CD8 T cell numbers and function after LCMV CL-13 infection. In contrast, PD-L1 expression on nonhematopoietic cells limited viral clearance and immunopathology in infected tissues. Together, these data demonstrate that there are distinct roles for PD-L1 on hematopoietic and nonhematopoietic cells in regulating CD8 T cell responses and viral clearance during chronic viral infection.
Copyright (C) 2010 The American Society for Clinical Investigation, Inc.
