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

SN Mueller, VK Vanguri, SJ Ha… - The Journal of …, 2010 - Am Soc Clin Investig
SN Mueller, VK Vanguri, SJ Ha, EE West, ME Keir, JN Glickman, AH Sharpe, R Ahmed
The Journal of clinical investigation, 2010Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation