Cytotoxic T-lymphocyte antigen 4 blockade augments the T-cell response primed by attenuated Listeria monocytogenes resulting in more rapid clearance of virulent bacterial challenge

Jared H. Rowe, Tanner M. Johanns, James M. Ertelt, Joseph C. Lai, Sing Sing Way

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) uniformly suppresses antigen-specific T cells during chronic infection with bacterial, parasitic or viral pathogens. However, the importance of CTLA-4 in controlling the T-cell response during acute infection or after priming with live attenuated vaccine vectors has not been well characterized. Since strategies aimed at blocking CTLA-4 are being actively developed to therapeutically augment T-cell-mediated immunity, the effects of CTLA-4 blockade on T-cell activation during these conditions need to be more clearly defined. We have examined the role of CTLA-4 in a prime-challenge model of acute bacterial infection using both attenuated and virulent strains of the intracellular bacterium Listeria monocytogenes. Although Foxp3+ CD4+ T cells are the predominant CTLA-4-expressing cell type in naïve mice, antigen-specific Foxp3 - CD4+ cells upregulate CTLA-4 expression after primary L. monocytogenes infection. Blockade of CTLA-4 results in increased numbers of L. monocytogenes-specific CD4 and CD8 T cells after primary infection with attenuated L. monocytogenes, and confers more rapid bacterial clearance after secondary challenge with virulent L. monocytogenes. Accordingly, CTLA-4 plays an important suppressive role in T-cell priming and protective immunity in a prime-challenge model of acute bacterial infection.

Original languageEnglish
Pages (from-to)e471-e478
JournalImmunology
Volume128
Issue number1 PART 2
DOIs
StatePublished - Sep 1 2009
Externally publishedYes

Keywords

  • Bacteria
  • Costimulation
  • Infection
  • T cell
  • Vaccine

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