Local Inflammatory Cues Regulate Differentiation and Persistence of CD8 + Tissue-Resident Memory T Cells

Cell Rep. 2017 Apr 4;19(1):114-124. doi: 10.1016/j.celrep.2017.03.031.

Abstract

Many pathogens initiate infection at mucosal surfaces, and tissue-resident memory T (Trm) cells play an important role in protective immunity, yet the tissue-specific signals that regulate Trm differentiation are poorly defined. During Yersinia infection, CD8+ T cell recruitment to areas of inflammation within the intestine is required for differentiation of the CD103-CD69+ Trm subset. Intestinal proinflammatory microenvironments have elevated interferon (IFN)-β and interleukin-12 (IL-12), which regulated Trm markers, including CD103. Type I interferon-receptor- or IL-12-receptor-deficient T cells functioned similarly to wild-type (WT) cells during infection; however, the inability of T cells to respond to inflammation resulted in defective differentiation of CD103-CD69+ Trm cells and reduced Trm persistence. Intestinal macrophages were the main producers of IFN-β and IL-12 during infection, and deletion of CCR2+ IL-12-producing cells reduced the size of the CD103- Trm population. These data indicate that intestinal inflammation drives phenotypic diversity and abundance of Trm cells for optimal tissue-specific immunity.

Keywords: CD103; IL-12; bacterial infection; tissue-resident memory T cells.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / metabolism
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Antiviral Agents / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation*
  • Immunologic Memory / immunology*
  • Inflammation / immunology*
  • Integrin alpha Chains / genetics
  • Integrin alpha Chains / metabolism
  • Interferons / metabolism
  • Interleukin-12 / metabolism
  • Intestines / immunology*
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Receptors, CCR2 / metabolism
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Yersinia pseudotuberculosis Infections / immunology*

Substances

  • Adjuvants, Immunologic
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • Antiviral Agents
  • CCR2 protein, human
  • CD69 antigen
  • Integrin alpha Chains
  • Lectins, C-Type
  • Receptors, CCR2
  • Transforming Growth Factor beta
  • alpha E integrins
  • Interleukin-12
  • Interferons