期刊
JOURNAL OF IMMUNOLOGY
卷 188, 期 5, 页码 2111-2117出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1102265
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资金
- National Institutes of Health [R01AI076357, R01AI079088, R21AI079873]
- American Cancer Society [RSG-08-186-01-LIB]
- American Heart Association
The manipulation of signals downstream of the TCR can have profound consequences for T cell development, function, and homeostasis. Diacylglycerol (DAG) produced after TCR stimulation functions as a secondary messenger and mediates the signaling to Ras-MEK-Erk and NF-kappa B pathways in T cells. DAG kinases (DGKs) convert DAG into phosphatidic acid, resulting in termination of DAG signaling. In this study, we demonstrate that DAG metabolism by DGKs can serve a crucial function in viral clearance upon lymphocytic choriomeningitis virus infection. Ag-specific CD8(+) T cells from DGK alpha(-/-) and DGK zeta(-/-) mice show enhanced expansion and increased cytokine production after lymphocytic choriomeningitis virus infection, yet DGK-deficient memory CD8(+) T cells exhibit impaired expansion after rechallenge. Thus, DGK activity plays opposing roles in the expansion of CD8(+) T cells during the primary and memory phases of the immune response, whereas consistently inhibiting antiviral cytokine production. The Journal of Immunology, 2012, 188: 2111-2117.
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