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- Title
PD-L1 has distinct functions in hematopoietic and nonhematopoietic cells in regulating T cell responses during chronic infection in mice.
- Authors
Mueller, Scott N.; Vanguri, Vijay K.; Sang-Jun Ha; West, Erin E.; Keir, Mary E.; Glickman, Jonathan N.; Sharpe, Arlene H.; Ahmed, Rafi; Ha, Sang-Jun
- 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.
- Subjects
HEMATOPOIETIC stem cells; T cells; LABORATORY mice; IMMUNOPATHOLOGY; IMMUNE response; LYMPHOCYTIC choriomeningitis virus; MOLECULAR cloning; ANIMAL experimentation; BONE marrow; CHRONIC diseases; LIGANDS (Biochemistry); MICE; RESEARCH funding; VIRUS diseases; LYMPHOCYTE count; VIRAL meningitis
- Publication
Journal of Clinical Investigation, 2010, Vol 120, Issue 7, p2508
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI40040