PDL-1 blockade impedes T cell expansion and protective immunity primed by attenuated Listeria monocytogenes.
Infection with attenuated Listeria monocytogenes (Lm) is a robust in vivo model for examining how Ag-specific T cells are primed, and subsequent challenge with virulent Lm allows for the protective effects of T cell priming to be quantified. Herein, we investigated the role of programmed death ligand 1 (PDL-1) in T cell priming and immunity conferred after primary infection with Lm DeltaactA followed by virulent Lm challenge. In striking contrast to the inhibitory role of PDL-1 on T cell immunity in other infection models, marked reductions in the magnitude of T cell expansion and the kinetics of T cell proliferation were observed with PDL-1 blockade after primary Lm DeltaactA infection. More importantly, PDL-1 blockade beginning before primary infection and maintained throughout the experiment resulted in delayed bacterial clearance and T cell expansion after secondary challenge with virulent Lm. These results indicate that for immunity to intracellular bacterial infection, PDL-1 plays an important stimulatory role for priming and expansion of protective T cells.
Rowe
Jared H
JH
Department of Pediatrics, Center for Infectious Disease and Microbiology Translational Research, University of Minnesota School of Medicine, Minneapolis, MN 55455, USA.
Johanns
Tanner M
TM
Ertelt
James M
JM
Way
Sing Sing
SS
D000818:Animals; D018122:B7-1 Antigen / Q000276:immunology / Q000502:physiology*; D060890:B7-H1 Antigen; D008089:Listeria monocytogenes / Q000276:immunology* / Q000472:pathogenicity; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D008562:Membrane Glycoproteins; D010455:Peptides