Lymphocytic Choriomeningitis Virus Clone 13 Infection Results in CD8 T Cell-Mediated Host Mortality in Diacylglycerol Kinase α-Deficient Mice

Diacylglycerol is a potent element of intracellular secondary signaling cascades whose production is enhanced by cell-surface receptor agonism and function is regulated by enzymatic degradation by diacylglycerol kinases (DGKs). In T cells, stringent regulation of the activity of this second messenge...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2023-05, Vol.210 (9), p.1281-1291
Main Authors: Kudek, Matthew R, Xin, Gang, Alson, Donia, Holzhauer, Sandra, Shen, Jian, Kasmani, Moujtaba Y, Riese, Matthew, Cui, Weiguo
Format: Article
Language:English
Subjects:
Animals
CD8-Positive T-Lymphocytes - metabolism
Clone Cells
Diacylglycerol Kinase - genetics
Diacylglycerol Kinase - metabolism
Diglycerides - metabolism
Lymphocytic Choriomeningitis - metabolism
Lymphocytic choriomeningitis virus
Mice
Mice, Inbred C57BL
Mice, Knockout
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Summary:Diacylglycerol is a potent element of intracellular secondary signaling cascades whose production is enhanced by cell-surface receptor agonism and function is regulated by enzymatic degradation by diacylglycerol kinases (DGKs). In T cells, stringent regulation of the activity of this second messenger maintains an appropriate balance between effector function and anergy. In this article, we demonstrate that DGKα is an indispensable regulator of TCR-mediated activation of CD8 T cells in lymphocytic choriomeningitis virus Clone 13 viral infection. In the absence of DGKα, Clone 13 infection in a murine model results in a pathologic, proinflammatory state and a multicellular immunopathologic host death that is predominantly driven by CD8 effector T cells.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.2101011