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

J Immunol. 2008 Jun 1;180(11):7553-7. doi: 10.4049/jimmunol.180.11.7553.

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 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-1 Antigen / immunology
  • B7-1 Antigen / physiology*
  • B7-H1 Antigen
  • Listeria monocytogenes / immunology*
  • Listeria monocytogenes / pathogenicity
  • Listeriosis / immunology*
  • Listeriosis / microbiology
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Peptides / antagonists & inhibitors
  • Peptides / immunology
  • Peptides / physiology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • B7-1 Antigen
  • B7-H1 Antigen
  • Cd274 protein, mouse
  • Membrane Glycoproteins
  • Peptides