@article {542281, title = {PD-L1 has distinct functions in hematopoietic and nonhematopoietic cells in regulating T cell responses during chronic infection in mice.}, journal = {J Clin Invest}, volume = {120}, number = {7}, year = {2010}, month = {2010 Jul}, pages = {2508-15}, 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.}, keywords = {Animals, Bone Marrow, Chronic Disease, Female, Ligands, Lymphocyte Count, Lymphocytic Choriomeningitis, Mice, Mice, Inbred C57BL, Mice, Knockout, T-Lymphocytes, Virus Diseases}, issn = {1558-8238}, doi = {10.1172/JCI40040}, author = {Mueller, Scott N and Vanguri, Vijay K and Ha, Sang-Jun and West, Erin E and Keir, Mary E and Glickman, Jonathan N and Sharpe, Arlene H and Ahmed, Rafi} }