Early T-bet promotes LFA1 upregulation required for CD8+ effector and memory T cell development

J Exp Med. 2023 Feb 6;220(2):e20191287. doi: 10.1084/jem.20191287. Epub 2022 Nov 29.

Abstract

The T-box transcription factor T-bet is regarded as a "master regulator" of CD4+ Th1 differentiation and IFN-γ production. However, in multiple models of infection, T-bet appears less critical for CD8+ T cell expansion and effector function. Here, we show that following vaccination with a replication-deficient strain of Toxoplasma gondii, CD8+ T cell expression of T-bet is required for optimal expansion of parasite-specific effector CD8+ T cells. Analysis of the early events associated with T cell activation reveals that the α chain of LFA1, CD11a, is a target of T-bet, and T-bet is necessary for CD8+ T cell upregulation of this integrin, which influences the initial priming of CD8+ effector T cells. We propose that the early expression of T-bet represents a T cell-intrinsic factor that optimizes T-DC interactions necessary to generate effector responses.

Publication types

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

MeSH terms

  • CD8-Positive T-Lymphocytes
  • Lymphocyte Activation*
  • Memory T Cells*
  • Transcriptional Activation
  • Up-Regulation

Substances

  • A-factor (Streptomyces)