PD-L1 has distinct functions in hematopoietic and nonhematopoietic cells in regulating T cell responses during chronic infection in mice
Scott N. Mueller, … , Arlene H. Sharpe, Rafi Ahmed
Scott N. Mueller, … , Arlene H. Sharpe, Rafi Ahmed
Published June 14, 2010
Citation Information: J Clin Invest. 2010;120(7):2508-2515. https://doi.org/10.1172/JCI40040.
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Research Article Immunology

PD-L1 has distinct functions in hematopoietic and nonhematopoietic cells in regulating T cell responses during chronic infection in mice

Abstract

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.

Authors

Scott N. Mueller, Vijay K. Vanguri, Sang-Jun Ha, Erin E. West, Mary E. Keir, Jonathan N. Glickman, Arlene H. Sharpe, Rafi Ahmed

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