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Nat Immunol. 2006 Nov;7(11):1166-73. Epub 2006 Oct 8.

T cell anergy is reversed by active Ras and is regulated by diacylglycerol kinase-alpha.

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  • 1Department of Pathology, Section of Hematology and Oncology, University of Chicago, Chicago, Illinois 60637, USA.

Erratum in

  • Nat Immunol. 2006 Dec;7(12):1343.

Abstract

T cell anergy has been correlated with defective signaling by the GTPase Ras, but causal and mechanistic data linking defective Ras activity with T cell anergy are lacking. Here we used adenoviral transduction to genetically manipulate nonproliferating T cells and show that active Ras restored interleukin 2 production and mitogen-activated protein kinase signaling in T cells that were made anergic in vitro or in vivo. Diacylglycerol kinases (DGKs), which negatively regulate Ras activity, were upregulated in anergic T cells, and a DGK inhibitor restored interleukin 2 production in anergic T cells. Both anergy and DGK-alpha overexpression were associated with defective translocation of the Ras guanine nucleotide-exchange factor RasGRP1 to the plasma membrane. Our data support a causal function for excess DGK activity and defective Ras signaling in T cell anergy.

PMID:
17028589
DOI:
10.1038/ni1394
[PubMed - indexed for MEDLINE]
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