Disruption of diacylglycerol metabolism impairs the induction of T cell anergy.

Published

Journal Article

Anergic T cells have altered diacylglycerol metabolism, but whether that altered metabolism has a causative function in the induction of T cell anergy is not apparent. To test the importance of diacylglycerol metabolism in T cell anergy, we manipulated diacylglycerol kinases (DGKs), which are enzymes that terminate diacylglycerol-dependent signaling. Overexpression of DGK-alpha resulted in a defect in T cell receptor signaling that is characteristic of anergy. We generated DGK-alpha-deficient mice and found that DGK-alpha-deficient T cells had more diacylglycerol-dependent T cell receptor signaling. In vivo anergy induction was impaired in DGK-alpha-deficient mice. When stimulated in anergy-producing conditions, T cells lacking DGK-alpha or DGK-zeta proliferated and produced interleukin 2. Pharmacological inhibition of DGK-alpha activity in DGK-zeta-deficient T cells that received an anergizing stimulus proliferated similarly to wild-type T cells that received CD28 costimulation and prevented anergy induction. Our findings suggest that regulation of diacylglycerol metabolism is critical in determining whether activation or anergy ensues after T cell receptor stimulation.

Full Text

Duke Authors

Cited Authors

  • Olenchock, BA; Guo, R; Carpenter, JH; Jordan, M; Topham, MK; Koretzky, GA; Zhong, X-P

Published Date

  • November 2006

Published In

Volume / Issue

  • 7 / 11

Start / End Page

  • 1174 - 1181

PubMed ID

  • 17028587

Pubmed Central ID

  • 17028587

Electronic International Standard Serial Number (EISSN)

  • 1529-2916

International Standard Serial Number (ISSN)

  • 1529-2908

Digital Object Identifier (DOI)

  • 10.1038/ni1400

Language

  • eng