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Intestinal CD4-CD8αβ-TCRαβ+ T cells function as tolerogenic antigen presenting cells in mice

ABSTRACT: To distinguish harmless from harmful antigens (Ag), anatomic, cellular and molecular mechanisms operate in the intestinal tract to acquire, process, present and interpret luminal Ags. The intestinal mucosa is populated by many T cell types in the intraepithelial lymphocytes (IEL) and lamina propria lymphocytes (LPL) populations, including double negative CD4-CD8αβ-TCRαβ+ T (double-negative T/DNT) cells. Here we show that murine DNT cells in the small intestine reach across the epithelial barrier to capture luminal Ags. A sizeable fraction of DNT cells in Peyer’s patches and mesenteric lymph nodes express MHC-II, but little or no classical co-stimulatory molecules. Indeed, DNT cells acquire, process and present antigenic proteins to tolerize Ag-specific CD4+ T cells. Conditional genetic ablation of MHC-II in T cells disable this tolerogenic function and rendered mutant mice hypersusceptible to intestinal inflammation. Intriguingly, intestinal T cells in patients with Crohn’s disease express lower levels of HLA-DR than those from controls. Our findings thus suggest that MHC-II+ DNT cells may regulate intestinal immune homeostasis and their dysfunction may contribute to the pathogenesis of inflammatory bowel disease.

ORGANISM(S): Mus musculus

PROVIDER: GSE298133 | GEO | 2025/07/09

REPOSITORIES: GEO

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