Lung injury induces a polarized immune response by self-antigen-specific CD4+ Foxp3+ regulatory T cells

Cell Rep. 2023 Aug 29;42(8):112839. doi: 10.1016/j.celrep.2023.112839. Epub 2023 Jul 20.

Abstract

Self-antigen-specific T cells are prevalent in the mature adaptive immune system but are regulated through multiple mechanisms of tolerance. However, inflammatory conditions such as tissue injury may allow these T cells to break tolerance and trigger autoimmunity. To understand how the T cell repertoire responds to the presentation of self-antigen under highly stimulatory conditions, we use peptide:major histocompatibility complex (MHC) class II tetramers to track the behavior of endogenous CD4+ T cells with specificity to a lung-expressed self-antigen in mouse models of immune-mediated lung injury. Acute injury results in the exclusive expansion of CD4+ regulatory T cells (Tregs) that is dependent on self-antigen recognition and interleukin-2 (IL-2). Conversely, conventional CD4+ T cells of the same self-antigen specificity remain unresponsive even following Treg ablation. Thus, the self-antigen-specific CD4+ T cell repertoire is poised to serve a regulatory function during acute tissue damage to limit further damage and the possibility of autoimmunity.

Keywords: CD4(+) T cell; CP: Immunology; Foxp3; T cell repertoire; Tregs; autoimmunity; epitope spreading; peptide:MHC tetramer; peripheral tolerance; regulatory T cell; self-antigen.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantigens
  • Autoimmunity
  • Forkhead Transcription Factors
  • Histocompatibility Antigens Class II
  • Lung Injury*
  • Mice
  • T-Lymphocytes, Regulatory*

Substances

  • Autoantigens
  • Histocompatibility Antigens Class II
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse