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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

Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA
Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA.
University of Michigan Crohn's and Colitis Program, Ann Arbor, Michigan, USA.
Consolidated Pathology Consultants, Northwestern Lake Forest Hospital, Lake Forest, Illinois, USA.
Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA.
Contributed equally


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.


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

[Available on 2019-12-20]

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