Regulatory T cells enforce self-nonself discrimination by constraining conventional T cells of matched self-specificity during infection

ABSTRACT: During infections, Foxp3+ regulatory T (Treg) cells must control autoreactive conventional T (Tconv) cell responses against self-peptide antigens while permitting those against pathogen-derived “nonself” peptides. We sought to define the basis of this selectivity using mice in which Tregs reactive to a single prostate-specific self-peptide/MHC (self-pMHC) antigen, termed "C4", were selectively depleted ("C4ΔTEC" mice). We demonstrated that Tregs reactive to the C4 peptide were dispensable for the control of Tconv cells of matched antigen specificity at homeostasis but were required to control such Tconv cells and prevent fulminant prostatic autoimmunity following infection with the pathogen L monocytogenes engineered to express the C4 peptide ("Lm[C4]"). We performed the experiment outlined here to understand how the absence of C4-specific Treg cells in C4ΔTEC mice changes the phenotypic state of the C4-specific Tconv cells following Lm[C4] infection to drive autoimmunity. We found that C4-specific Tconv cells adopted preferential and differential cell states in both C4ΔTEC mice and wild-type mice that have C4-specific Treg cells. Specifically, gene expesion data revealed that C4-specific Tconv cells in wild-type mice preferentially adopted a non-proliferating effector state, while C4-specific Tconv in C4ΔTEC mice appeared as proliferating effector cells and proliferating central-memory cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE235974 | GEO | 2025/04/23

REPOSITORIES: GEO