PD-L1 has distinct functions in hematopoietic and nonhematopoietic cells in regulating T cell responses during chronic infection in mice.
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.
Mueller
Scott N
SN
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA. smue@unimelb.edu.au
Vanguri
Vijay K
VK
Ha
Sang-Jun
SJ
West
Erin E
EE
Keir
Mary E
ME
Glickman
Jonathan N
JN
Sharpe
Arlene H
AH
Ahmed
Rafi
R
D000818:Animals; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology / Q000821:virology; D002908:Chronic Disease; D005260:Female; D008024:Ligands; D018655:Lymphocyte Count; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology; D014777:Virus Diseases / Q000276:immunology* / Q000473:pathology / Q000821:virology
D008024:Ligands