Proinflammatory microenvironments within the intestine regulate the differentiation of tissue-resident CD8⁺ T cells responding to infection

Nat Immunol. 2015 Apr;16(4):406-14. doi: 10.1038/ni.3108. Epub 2015 Feb 23.

Abstract

We report that oral infection with Yersinia pseudotuberculosis results in the development of two distinct populations of pathogen-specific CD8(+) tissue-resident memory T cells (TRM cells) in the lamina propria. CD103(-) T cells did not require transforming growth factor-β (TGF-β) signaling but were true resident memory cells. Unlike CD103(+)CD8(+) T cells, which were TGF-β dependent and were scattered in the tissue, CD103(-)CD8(+) T cells clustered with CD4(+) T cells and CX3CR1(+) macrophages and/or dendritic cells around areas of bacterial infection. CXCR3-dependent recruitment of cells to inflamed areas was critical for development of the CD103(-) population and pathogen clearance. Our studies have identified the 'preferential' development of CD103(-) TRM cells in inflammatory microenvironments within the lamina propria and suggest that this subset has a critical role in controlling infection.

Publication types

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

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / microbiology
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / microbiology
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Movement
  • Cellular Microenvironment
  • Dendritic Cells / immunology
  • Dendritic Cells / microbiology
  • Dendritic Cells / pathology
  • Gene Expression Regulation
  • Immunologic Memory
  • Immunophenotyping
  • Integrin alpha Chains / deficiency
  • Integrin alpha Chains / genetics
  • Integrin alpha Chains / immunology*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology
  • Macrophages / immunology
  • Macrophages / microbiology
  • Macrophages / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, CXCR3 / genetics
  • Receptors, CXCR3 / immunology
  • Signal Transduction
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / immunology
  • Yersinia pseudotuberculosis / immunology
  • Yersinia pseudotuberculosis Infections / genetics
  • Yersinia pseudotuberculosis Infections / immunology*
  • Yersinia pseudotuberculosis Infections / microbiology
  • Yersinia pseudotuberculosis Infections / pathology

Substances

  • Antigens, CD
  • Cxcr3 protein, mouse
  • Integrin alpha Chains
  • Receptors, CXCR3
  • Transforming Growth Factor beta
  • alpha E integrins