1. PD-L1 has distinct functions in hematopoietic and nonhematopoietic cells in regulating T cell responses during chronic infection in mice.
- Author
-
Mueller, Scott N., Vanguri, Vijay K., Sang-Jun Ha, West, Erin E., Keir, Mary E., Glickman, Jonathan N., Sharpe, Arlene H., Ahmed, Rafi, and Ha, Sang-Jun
- 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 - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF