| First Author | Olenchock BA | Year | 2006 |
| Journal | Nat Immunol | Volume | 7 |
| Issue | 11 | Pages | 1174-81 |
| PubMed ID | 17028587 | Mgi Jnum | J:113564 |
| Mgi Id | MGI:3686960 | Doi | 10.1038/ni1400 |
| Citation | Olenchock BA, et al. (2006) Disruption of diacylglycerol metabolism impairs the induction of T cell anergy. Nat Immunol 7(11):1174-81 |
| abstractText | 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. |
