title: Differential regulation of primary and memory CD8 T cell immune responses by diacylglycerol kinases.
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.
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Jinwook
authors.initials: J
authors.lastname: Shin
authors.forename: Thomas F
authors.initials: TF
authors.lastname: O'Brien
authors.forename: Jason M
authors.initials: JM
authors.lastname: Grayson
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Zhong
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000037:antagonists & inhibitors / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology* / Q000276:immunology* / Q000821:virology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells; D006224:Cricetinae; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D019852:Diacylglycerol Kinase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007156:Immunologic Memory / Q000235:genetics; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D019852:Diacylglycerol Kinase; C512480:diacylglycerol kinase zeta, mouse