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

Published

Journal Article

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.

Full Text

Cited Authors

  • Zha, Y; Marks, R; Ho, AW; Peterson, AC; Janardhan, S; Brown, I; Praveen, K; Stang, S; Stone, JC; Gajewski, TF

Published Date

  • November 2006

Published In

Volume / Issue

  • 7 / 11

Start / End Page

  • 1166 - 1173

PubMed ID

  • 17028589

Pubmed Central ID

  • 17028589

Electronic International Standard Serial Number (EISSN)

  • 1529-2916

International Standard Serial Number (ISSN)

  • 1529-2908

Digital Object Identifier (DOI)

  • 10.1038/ni1394

Language

  • eng