Culling of activated CD4 T cells during typhoid is driven by Salmonella virulence genes

J Immunol. 2009 Jun 15;182(12):7838-45. doi: 10.4049/jimmunol.0900382.

Abstract

Pathogen-specific CD4 T cells are activated within a few hours of oral Salmonella infection and are essential for protective immunity. However, CD4 T cells do not participate in bacterial clearance until several weeks after infection, suggesting that Salmonella can inhibit or evade CD4 T cells that are activated at early time points. Here, we describe the progressive culling of initially activated CD4 T cells in Salmonella-infected mice. Loss of activated CD4 T cells was independent of early instructional programming, T cell precursor frequency, and Ag availability. In contrast, apoptosis of Ag-specific CD4 T cells was actively induced by live bacteria in a process that required Salmonella pathogenicity island-2 and correlated with increased expression of PD-L1. These data demonstrate efficient culling of initially activated Ag-specific CD4 cells by a microbial pathogen and document a novel strategy for bacterial immune evasion.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis
  • B7-1 Antigen / immunology
  • B7-H1 Antigen
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Separation / methods*
  • Lymphocyte Activation / immunology*
  • Membrane Glycoproteins / immunology
  • Mice
  • Mice, Inbred C57BL
  • O Antigens / genetics
  • O Antigens / immunology*
  • O Antigens / metabolism
  • Peptides / immunology
  • Salmonella / genetics
  • Salmonella / immunology*
  • Salmonella / metabolism
  • Salmonella / pathogenicity*
  • Typhoid Fever / immunology*
  • Virulence

Substances

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