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

Publication ,  Journal Article
Olenchock, BA; Guo, R; Carpenter, JH; Jordan, M; Topham, MK; Koretzky, GA; Zhong, X-P
Published in: Nat Immunol
November 2006

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.

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Published In

Nat Immunol

DOI

ISSN

1529-2908

Publication Date

November 2006

Volume

7

Issue

11

Start / End Page

1174 / 1181

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Receptors, Antigen, T-Cell
  • Mice, Knockout
  • Mice
  • Lymphocyte Activation
  • Immunology
  • Diglycerides
  • Diacylglycerol Kinase
  • Clonal Anergy
  • Animals
 

Citation

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Olenchock, B. A., Guo, R., Carpenter, J. H., Jordan, M., Topham, M. K., Koretzky, G. A., & Zhong, X.-P. (2006). Disruption of diacylglycerol metabolism impairs the induction of T cell anergy. Nat Immunol, 7(11), 1174–1181. https://doi.org/10.1038/ni1400
Olenchock, Benjamin A., Rishu Guo, Jeffery H. Carpenter, Martha Jordan, Matthew K. Topham, Gary A. Koretzky, and Xiao-Ping Zhong. “Disruption of diacylglycerol metabolism impairs the induction of T cell anergy.Nat Immunol 7, no. 11 (November 2006): 1174–81. https://doi.org/10.1038/ni1400.
Olenchock BA, Guo R, Carpenter JH, Jordan M, Topham MK, Koretzky GA, et al. Disruption of diacylglycerol metabolism impairs the induction of T cell anergy. Nat Immunol. 2006 Nov;7(11):1174–81.
Olenchock, Benjamin A., et al. “Disruption of diacylglycerol metabolism impairs the induction of T cell anergy.Nat Immunol, vol. 7, no. 11, Nov. 2006, pp. 1174–81. Pubmed, doi:10.1038/ni1400.
Olenchock BA, Guo R, Carpenter JH, Jordan M, Topham MK, Koretzky GA, Zhong X-P. Disruption of diacylglycerol metabolism impairs the induction of T cell anergy. Nat Immunol. 2006 Nov;7(11):1174–1181.

Published In

Nat Immunol

DOI

ISSN

1529-2908

Publication Date

November 2006

Volume

7

Issue

11

Start / End Page

1174 / 1181

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Receptors, Antigen, T-Cell
  • Mice, Knockout
  • Mice
  • Lymphocyte Activation
  • Immunology
  • Diglycerides
  • Diacylglycerol Kinase
  • Clonal Anergy
  • Animals