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Infect Immun. 2019 Jun 20;87(7). pii: e00295-19. doi: 10.1128/IAI.00295-19. Print 2019 Jul.

Citrobacter rodentium Induces Tissue-Resident Memory CD4+ T Cells.

Author information

1
Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA bishus@med.umich.edu.
2
Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA.
3
University of Michigan Crohn's and Colitis Program, Ann Arbor, Michigan, USA.
4
Consolidated Pathology Consultants, Northwestern Lake Forest Hospital, Lake Forest, Illinois, USA.
5
Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
6
Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA.
#
Contributed equally

Abstract

Tissue-resident memory T cells (TRM cells) are a novel population of tissue-restricted antigen-specific T cells. TRM cells are induced by pathogens and promote host defense against secondary infections. Although TRM cells cannot be detected in circulation, they are the major memory CD4+ and CD8+ T-cell population in tissues in mice and humans. Murine models of CD8+ TRM cells have shown that CD8+ TRM cells maintain tissue residency via CD69 and though tumor growth factor β-dependent induction of CD103. In contrast to CD8+ TRM cells, there are few models of CD4+ TRM cells. Thus, much less is known about the factors regulating the induction, maintenance, and host defense functions of CD4+ TRM cells. Citrobacter rodentium is known to induce IL-17+ and IL-22+ CD4+ T cells (Th17 and Th22 cells, respectively). Moreover, data from IL-22 reporter mice show that most IL-22+ cells in the colon 3 months after C. rodentium infection are CD4+ T cells. This collectively suggests that C. rodentium may induce CD4+ TRM cells. Here, we demonstrate that C. rodentium induces a population of IL-17A+ CD4+ T cells that are tissue restricted and antigen specific, thus meeting the criteria of CD4+ TRM cells. These cells expand and are a major source of IL-22 during secondary C. rodentium infection, even before the T-cell phase of the host response in primary infection. Finally, using FTY 720, which depletes circulating naive and effector T cells but not tissue-restricted T cells, we show that these CD4+ TRM cells can promote host defense.

KEYWORDS:

CD4+; Citrobacter; T cells; colitis; tissue-resident memory

PMID:
31061145
PMCID:
PMC6589064
[Available on 2019-12-20]
DOI:
10.1128/IAI.00295-19

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