Bibliographic Details
| Title: |
Disruption of diacylglycerol metabolism impairs the induction of T cell anergy. |
| Authors: |
Olenchock, Benjamin A.1, Guo, Rishu2, Carpenter, Jeffery H.2, Jordan, Martha1, Topham, Matthew K.3, Koretzky, Gary A.1,4 koretzky@mail.med.upenn.edu, Xiao-Ping Zhong2,5 zhong001@mc.duke.edu |
| Source: |
Nature Immunology. Nov2006, Vol. 7 Issue 11, p1174-1181. 8p. 8 Graphs. |
| Subject Terms: |
*T cells, *DIGLYCERIDES, *T cell receptors, *INTERLEUKIN-2, *PROTEIN-tyrosine kinases, *CELL proliferation |
| Abstract: |
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-α resulted in a defect in T cell receptor signaling that is characteristic of anergy. We generated DGK-α-deficient mice and found that DGK-α-deficient T cells had more diacylglycerol-dependent T cell receptor signaling. In vivo anergy induction was impaired in DGK-α-deficient mice. When stimulated in anergy-producing conditions, T cells lacking DGK-α or DGK-ζ proliferated and produced interleukin 2. Pharmacological inhibition of DGK-α activity in DGK-ζ-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. [ABSTRACT FROM AUTHOR] |
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| Database: |
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