Citrobacter rodentium Induces Tissue-Resident Memory CD4 ⁺ T Cells

Abstract

Tissue-resident memory T cells (T RM cells) are a novel population of tissue-restricted antigen-specific T cells. T RM cells are induced by pathogens and promote host defense against secondary infections. Although T RM cells cannot be detected in circulation, they are the major memory CD4 ϩ and CD8 ϩ T-cell population in tissues in mice and humans. Murine models of CD8 ϩ T RM cells have shown that CD8 ϩ T RM cells maintain tissue residency via CD69 and though tumor growth factor ␤-dependent induction of CD103. In contrast to CD8 ϩ T RM cells, there are few models of CD4 ϩ T RM cells. Thus, much less is known about the factors regulating the induction, maintenance, and host defense functions of CD4 ϩ T RM cells. Citrobacter rodentium is known to induce IL-17 ϩ and IL-22 ϩ CD4 ϩ T cells (T h 17 and T h 22 cells, respectively). Moreover, data from IL-22 reporter mice show that most IL-22 ϩ cells in the colon 3 months after C. rodentium infection are CD4 ϩ T cells. This collectively suggests that C. rodentium may induce CD4 ϩ T RM cells. Here, we demonstrate that C. rodentium induces a population of IL-17A ϩ CD4 ϩ T cells that are tissue restricted and antigen specific, thus meeting the criteria of CD4 ϩ T RM 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 ϩ T RM cells can promote host defense.

Generation of protective pneumococcal-specific nasal resident memory CD4+ T cells via parenteral immunization

“…A protective role for CD4 + T RM at mucosal surfaces has recently been described for a number of bacterial pathogens of public health significance. 1,2,[28][29][30][31][32][33][34] Exposure to live pneumococcus in the nasopharynx protects mice against subsequent homologous or heterologous pneumococcal challenge. 21,22 Hence, we hypothesized that I.N.…”

T Cell Immunity to Bacterial Pathogens: Mechanisms of Immune Control and Bacterial Evasion

“…However, CD4 + T RM cells lack, or possess low levels of, CD103 and can depend on receiving different signals (e.g., antigen), even in the same anatomical site [ 135 , 136 , 137 , 138 ]. Research in the past decade determined that CD4 + T RM cells are induced at various mucosal sites to mediate protective immunity against an array of bacterial pathogens, including M. tuberculosis [ 139 ], B. pertussis [ 140 ], S. pneumoniae [ 141 ], L. monocytogenes [ 142 ], C. rodentium [ 143 ], and Chlamydia trachomatis [ 144 ]. Despite this, less is known about CD4 + T RM cells in infection settings, in comparison to their CD8 + T RM cell counterparts, or whether CD4 + T RM cells form effector T H cell subtypes, such as T H 1, T H 2, and T H 17, or even T FH cells.…”

PIR-B Regulates CD4+ IL17a+ T-Cell Survival and Restricts T-Cell–Dependent Intestinal Inflammatory Responses

“…We and others have identified an increased frequency of CD4 þ TRM T cells with a proinflammatory Th17 phenotype in biopsy samples from active CD and ulcerative colitis patients compared with healthy control patients. 17,18,57,58 Furthermore, increased levels of CD69 þ CD103 þ CD4 þ TRM T cells have been associated with clinical flares. 18 Previous reports identified a link between CD4 þ TRM IL17A þ T cells and CD by using biopsy specimens from CD patients undergoing surgery for severe, chronically active, or complicated disease.…”