PDL-1 blockade impedes T cell expansion and protective immunity primed by attenuated Listeria monocytogenes

JH Rowe, TM Johanns, JM Ertelt… - The Journal of …, 2008 - journals.aai.org
JH Rowe, TM Johanns, JM Ertelt, SS Way
The Journal of Immunology, 2008journals.aai.org
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 ΔactA 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 …
Abstract
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 ΔactA 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 ΔactA 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.
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