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Differential regulation of primary and memory CD8 T cell immune responses by diacylglycerol kinases.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2012 Mar 01; Vol. 188 (5), pp. 2111-7. Date of Electronic Publication: 2012 Jan 23. - Publication Year :
- 2012
-
Abstract
- 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-κB 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 DGKα(-/-) and DGKζ(-/-) 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.
- Subjects :
- Animals
Antiviral Agents antagonists & inhibitors
Antiviral Agents metabolism
CD8-Positive T-Lymphocytes virology
Cell Differentiation genetics
Cell Differentiation immunology
Cell Line
Clone Cells
Cricetinae
Cytokines antagonists & inhibitors
Cytokines biosynthesis
Diacylglycerol Kinase deficiency
Diacylglycerol Kinase genetics
Disease Models, Animal
Down-Regulation genetics
Down-Regulation immunology
Epitopes, T-Lymphocyte immunology
Lymphocytic Choriomeningitis genetics
Lymphocytic choriomeningitis virus immunology
Mice
Mice, Knockout
Mice, Transgenic
CD8-Positive T-Lymphocytes enzymology
CD8-Positive T-Lymphocytes immunology
Diacylglycerol Kinase physiology
Immunologic Memory genetics
Lymphocytic Choriomeningitis immunology
Lymphocytic Choriomeningitis pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 188
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 22271650
- Full Text :
- https://doi.org/10.4049/jimmunol.1102265