Autoimmune CD4⁺ T cells fine-tune TCF1 expression to maintain function and survive persistent antigen exposure during diabetes.

ABSTRACT: Self-reactive T cells experience chronic antigen exposure but do not exhibit signs of exhaustion. Here, we investigated the mechanisms for sustained, functioning autoimmune CD4⁺ T cells despite chronic stimulation. Examination of T cell priming showed that CD4⁺ T cells activated in the absence of infectious signals retained TCF1 expression. At later time points and during blockade of new T cell recruitment, most islet-infiltrating autoimmune CD4⁺ T cells were TCF1⁺, although expression was reduced on a per T cell basis. The Tcf7 locus was epigenetically modified in circulating autoimmune CD4⁺ T cells, suggesting a pre-programmed de novo methylation of the locus in early stages of autoimmune CD4⁺ T cell differentiation. This

SUBMITTER: Aljobaily N 

PROVIDER: S-EPMC11563894 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature