Effector CD4 T cells with progenitor potential mediate chronic intestinal inflammation

Abstract

Dysregulated CD4 T cell responses are causally linked to autoimmune and chronic inflammatory disorders, yet the cellular attributes responsible for maintaining the disease remain poorly understood. Herein, we identify a discrete population of effector CD4 T cells that is able to both sustain and confer intestinal inflammation. This subset of pathogenic CD4 T cells possesses a unique gene signature consistent with self-renewing T cells and hematopoietic progenitor cells, exhibits enhanced survival, and continually seeds the terminally differentiated IFNγ-producing cells in the inflamed intestine. Mechanistically, this population selectively expresses the glycosyltransferase ST6Gal-I, which is required for optimal expression of the stemness-associated molecule TCF1 by effector CD4 T cells. Our findings indicate that the chronicity of T cell–mediated inflammation is perpetuated by specific effector CD4 T cells with stem-like properties.