Requirement for T-bet in the aberrant differentiation of unhelped memory CD8+ T cells. Academic Article uri icon

Overview

abstract

  • Immunity to intracellular pathogens requires dynamic balance between terminal differentiation of short-lived, cytotoxic effector CD8+ T cells and self-renewal of central-memory CD8+ T cells. We now show that T-bet represses transcription of IL-7Ralpha and drives differentiation of effector and effector-memory CD8+ T cells at the expense of central-memory cells. We also found T-bet to be overexpressed in CD8+ T cells that differentiated in the absence of CD4+ T cell help, a condition that is associated with defective central-memory formation. Finally, deletion of T-bet corrected the abnormal phenotypic and functional properties of "unhelped" memory CD8+ T cells. T-bet, thus, appears to function as a molecular switch between central- and effector-memory cell differentiation. Antagonism of T-bet may, therefore, represent a novel strategy to offset dysfunctional programming of memory CD8+ T cells.

publication date

  • August 13, 2007

Research

keywords

  • CD8-Positive T-Lymphocytes
  • Cell Differentiation
  • Immunologic Memory
  • T-Box Domain Proteins
  • T-Lymphocyte Subsets
  • T-Lymphocytes, Helper-Inducer

Identity

PubMed Central ID

  • PMC2118697

Scopus Document Identifier

  • 34548402098

Digital Object Identifier (DOI)

  • 10.1084/jem.20070841

PubMed ID

  • 17698591

Additional Document Info

volume

  • 204

issue

  • 9