NDLI: Antigenic experience dictates functional role of glycogen synthase kinase-3 in human CD4+ T cell responses.

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Antigenic experience dictates functional role of glycogen synthase kinase-3 in human CD4+ T cell responses.

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Antigenic experience dictates functional role of glycogen synthase kinase-3 in human CD4+ T cell responses.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Benakanakere, Manjunatha R. Garcia, Carlos A. Kinane, Denis F. Martin, Michael Alard, Pascale Kosiewicz, Michelle M.
Description	Country affiliation: United States Author Affiliation: Garcia CA ( Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40292, USA.)
Abstract	Signals induced by the TCR and CD28 costimulatory pathway have been shown to lead to the inactivation of the constitutively active enzyme, glycogen synthase kinase-3 (GSK3), which has been implicated in the regulation of IL-2 and T cell proliferation. However, it is unknown whether GSK3 plays a similar role in naive and memory CD4(+) T cell responses. Here we demonstrate a divergence in the dependency on the inactivation of GSK3 in the proliferative responses of human naive and memory CD4(+) T cells. We find that although CD28 costimulation increases the frequency of phospho-GSK3 inactivation in TCR-stimulated naive and memory CD4(+) T cells, memory cells are less reliant on GSK3 inactivation for their proliferative responses. Rather we find that GSK3beta plays a previously unrecognized role in the selective regulation of the IL-10 recall response by human memory CD4(+) T cells. Furthermore, GSK3beta-inactivated memory CD4(+) T cells acquired the capacity to suppress the bystander proliferation of CD4(+) T cells in an IL-10-dependent, cell contact-independent manner. Our findings reveal a dichotomy present in the function of GSK3 in distinct human CD4(+) T cell populations.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	12
Volume Number	181
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2008-12-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cd4-positive T-lymphocytes Enzymology Immunology Glycogen Synthase Kinase 3 Physiology Immunologic Memory Bystander Effect Cytology Metabolism Cell Proliferation Cells, Cultured Antagonists & Inhibitors Interleukin-10 Biosynthesis Lymphocyte Activation Lymphocyte Count G0 Phase Signal Transduction T-lymphocyte Subsets Comparative Study Research Support, N.i.h., Extramural Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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Antigenic Experience Dictates Functional Role of Glycogen Synthase Kinase-3 in Human CD4+ T Cell Responses1

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Antigenic experience dictates functional role of glycogen synthase kinase-3 in human CD4+ T cell responses.

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Antigenic Experience Dictates Functional Role of Glycogen Synthase Kinase-3 in Human CD4+ T Cell Responses1

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