Differential regulation of primary and memory CD8 T cell immune responses by diacylglycerol kinases
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 kina...
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| Veröffentlicht in: | The Journal of immunology (1950) 2012-03, Vol.188 (5), p.2111-2117 |
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| container_title | The Journal of immunology (1950) |
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| creator | Shin, Jinwook O'Brien, Thomas F Grayson, Jason M Zhong, Xiao-Ping |
| description | 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. |
| doi_str_mv | 10.4049/jimmunol.1102265 |
| format | Article |
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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. 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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.</description><subject>Animals</subject><subject>Antiviral Agents - antagonists & inhibitors</subject><subject>Antiviral Agents - metabolism</subject><subject>CD8-Positive T-Lymphocytes - enzymology</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - virology</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Differentiation - immunology</subject><subject>Cell Line</subject><subject>Clone Cells</subject><subject>Cricetinae</subject><subject>Cytokines - antagonists & inhibitors</subject><subject>Cytokines - biosynthesis</subject><subject>Diacylglycerol Kinase - deficiency</subject><subject>Diacylglycerol Kinase - genetics</subject><subject>Diacylglycerol Kinase - physiology</subject><subject>Disease Models, Animal</subject><subject>Down-Regulation - genetics</subject><subject>Down-Regulation - immunology</subject><subject>Epitopes, T-Lymphocyte - immunology</subject><subject>Immunologic Memory - genetics</subject><subject>Lymphocytic Choriomeningitis - genetics</subject><subject>Lymphocytic Choriomeningitis - immunology</subject><subject>Lymphocytic Choriomeningitis - pathology</subject><subject>Lymphocytic choriomeningitis virus</subject><subject>Lymphocytic choriomeningitis virus - immunology</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mice, Transgenic</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUT1P7DAQtNBDcHz0VMjdqwL2xl9pnoSOTwmJBmrLcZzD4MSHfUG6f4-BAz06ql3tzszuaBA6ouSEEdacPvlhmMYYTiglAIJvoRnlnFRCEPEHzUgZVlQKuYv2cn4ihAgCbAftAoCkgpMZsue-711y48qbgJNbTMGsfBxx7PEy-cGkNTZjhwc3xNLOzxW-x9aFgD9Ou0LJyzhml3G7xp03dh0WYW1digE_-9GUzQHa7k3I7nBT99HD5cX9_Lq6vbu6mZ_dVpaBXFXMQC3ASmVkxxXvuKFMctkoYAxoa43lVEALXW-BdkK2nJAGGhCCkZr3pt5H_z51l1M7uM4WU8kEvbGho_H652b0j3oRX3UNSknFi8DfjUCKL5PLKz34_G7WjC5OWZdbStWNEr9AAmtUw-qCJJ9Im2LOyfXf_1Ci30PUXyHqTYiFcvy_j2_CV2r1G-o2m0s</recordid><startdate>20120301</startdate><enddate>20120301</enddate><creator>Shin, Jinwook</creator><creator>O'Brien, Thomas F</creator><creator>Grayson, Jason M</creator><creator>Zhong, Xiao-Ping</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7T5</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20120301</creationdate><title>Differential regulation of primary and memory CD8 T cell immune responses by diacylglycerol kinases</title><author>Shin, Jinwook ; O'Brien, Thomas F ; Grayson, Jason M ; Zhong, Xiao-Ping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c427t-4a2362c78a7d585d5a147579824421bcac5162b2dfc21d67b5009292664035fa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Antiviral Agents - antagonists & inhibitors</topic><topic>Antiviral Agents - metabolism</topic><topic>CD8-Positive T-Lymphocytes - enzymology</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>CD8-Positive T-Lymphocytes - virology</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Differentiation - immunology</topic><topic>Cell Line</topic><topic>Clone Cells</topic><topic>Cricetinae</topic><topic>Cytokines - antagonists & inhibitors</topic><topic>Cytokines - biosynthesis</topic><topic>Diacylglycerol Kinase - deficiency</topic><topic>Diacylglycerol Kinase - genetics</topic><topic>Diacylglycerol Kinase - physiology</topic><topic>Disease Models, Animal</topic><topic>Down-Regulation - genetics</topic><topic>Down-Regulation - immunology</topic><topic>Epitopes, T-Lymphocyte - immunology</topic><topic>Immunologic Memory - genetics</topic><topic>Lymphocytic Choriomeningitis - genetics</topic><topic>Lymphocytic Choriomeningitis - immunology</topic><topic>Lymphocytic Choriomeningitis - pathology</topic><topic>Lymphocytic choriomeningitis virus</topic><topic>Lymphocytic choriomeningitis virus - immunology</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Mice, Transgenic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shin, Jinwook</creatorcontrib><creatorcontrib>O'Brien, Thomas F</creatorcontrib><creatorcontrib>Grayson, Jason M</creatorcontrib><creatorcontrib>Zhong, Xiao-Ping</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shin, Jinwook</au><au>O'Brien, Thomas F</au><au>Grayson, Jason M</au><au>Zhong, Xiao-Ping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Differential regulation of primary and memory CD8 T cell immune responses by diacylglycerol kinases</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2012-03-01</date><risdate>2012</risdate><volume>188</volume><issue>5</issue><spage>2111</spage><epage>2117</epage><pages>2111-2117</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><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. 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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Animals Antiviral Agents - antagonists & inhibitors Antiviral Agents - metabolism CD8-Positive T-Lymphocytes - enzymology CD8-Positive T-Lymphocytes - immunology 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 Diacylglycerol Kinase - physiology Disease Models, Animal Down-Regulation - genetics Down-Regulation - immunology Epitopes, T-Lymphocyte - immunology Immunologic Memory - genetics Lymphocytic Choriomeningitis - genetics Lymphocytic Choriomeningitis - immunology Lymphocytic Choriomeningitis - pathology Lymphocytic choriomeningitis virus Lymphocytic choriomeningitis virus - immunology Mice Mice, Knockout Mice, Transgenic |
| title | Differential regulation of primary and memory CD8 T cell immune responses by diacylglycerol kinases |
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