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J Exp Med. 2007 Sep 3;204(9):2015-21. Epub 2007 Aug 13.

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

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1
Abramson Family Cancer Research Institute, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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.

PMID:
17698591
PMCID:
PMC2118697
DOI:
10.1084/jem.20070841
[Indexed for MEDLINE]
Free PMC Article
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