Abstract
Stimulation of the TCR leads to an oscillatory release of free calcium that activates members of the calcium/calmodulin-dependent protein kinase II (CaMKII) family. The CaMKII molecules have profound and lasting effects on cellular signaling in several cell types, yet the role of CaMKII in T cells is still poorly characterized. In this report we describe a splice variant of CaMKIIbeta, CaMKIIbeta'e, in mouse T cells. We have determined its function, along with that of CaMKIIgamma, by introducing the active and kinase-dead mutants into activated P14 TCR transgenic T cells using retroviral transduction. Active CaMKII enhanced the proliferation and cytotoxic activity of T cells while reducing their IL-2 production. Furthermore, it induced a profound state of unresponsiveness that could be overcome only by prolonged culture in IL-2. These results indicate that members of the CaMKII family play an important role in regulation of CD8 T cell proliferation, cytotoxic effector function, and the response to restimulation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alternative Splicing
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Animals
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Antigens / immunology
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CD4-Positive T-Lymphocytes / enzymology*
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CD4-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / enzymology*
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases / biosynthesis
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Calcium-Calmodulin-Dependent Protein Kinases / genetics
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Calcium-Calmodulin-Dependent Protein Kinases / physiology*
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Cell Proliferation
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Cell Survival / genetics
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Cell Survival / immunology
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Clonal Anergy / genetics
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Clonal Anergy / immunology*
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Cytokines / biosynthesis
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Cytotoxicity, Immunologic / genetics
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Enzyme Activation / genetics
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Enzyme Activation / immunology
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Isoenzymes / biosynthesis
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Isoenzymes / genetics
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Isoenzymes / physiology
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Lymphocyte Activation / genetics
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Lymphocyte Activation / immunology*
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Multienzyme Complexes / biosynthesis
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Multienzyme Complexes / genetics
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Multienzyme Complexes / physiology*
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Transduction, Genetic
Substances
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Antigens
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Cytokines
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Isoenzymes
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Multienzyme Complexes
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases