Diacylglycerol kinase α activity promotes survival of CD4+ 8+ double positive cells during thymocyte development

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Abstract
The diacylglycerol kinases (DGK) form a family of isoenzymes that catalyse the conversion of diacylglycerol (DAG) to phosphatidic acid (PA), both powerful second messengers in the cell. DGKα is expressed in brain, peripheral T cells and thymocytes and has been shown to translocate to the nuclear matrix upon T-cell receptor (TCR) engagement. Here, we show that high level expression of DGKα is induced following a signal transmitted through the pre-TCR and the protein tyrosine kinase, lck. Activity of DGKα contributes to survival in CD4+ 8+ (DP) thymocytes as pharmacological inhibition of DGK activity results in death of this cell population both in cell suspension and thymic explants. DGKα promotes survival in these thymocytes through a Bcl-regulated pathway. A consequence of inhibition of DGKα is the specific down-regulation of Bcl-xl, whereas in transgenic mice that over-express Bcl-2, death induced by the inhibitor is partially blocked. Thus we report a novel activity of DGKα in survival of thymocytes immediately after entry into the DP stage in development.