Intestinal damage is required for the pro-inflammatory differentiation of commensal CBir1-specific T cells

Mucosal Immunol. 2024 Feb;17(1):81-93. doi: 10.1016/j.mucimm.2023.11.001. Epub 2023 Nov 10.


Commensal-specific clusters of differentiation (CD)4+ T cells are expanded in patients with inflammatory bowel disease (IBD) compared to healthy individuals. How and where commensal-specific CD4+ T cells get activated is yet to be fully understood. We used CBir1 TCR-transgenic CD4+ T cells, specific to a commensal bacterial antigen, and different mouse models of IBD to characterize the dynamics of commensal-specific CD4+ T-cells activation. We found that CBir1 T cells proliferate following intestinal damage and cognate antigen presentation is mediated by CD11c+ cells in the colon-draining mesenteric lymph nodes. Using assay for transposase-accessible chromatin sequencing and flow cytometry, we showed that activated CBir1 T cells preferentially acquire an effector rather than regulatory phenotype, which is plastic over time. Moreover, CBir1 T cells, while insufficient to initiate intestinal inflammation, contributed to worse disease outcomes in the presence of other CD4+ T cells. Our results suggest that the commensal-specific T-cell responses observed in IBD exacerbate rather than initiate disease.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes
  • Cell Differentiation
  • Flow Cytometry
  • Humans
  • Inflammatory Bowel Diseases*
  • Intestines
  • Mice
  • T-Lymphocytes*