NDLI: Th2-specific immunity and function of peripheral T cells is regulated by the p56Lck Src homology 3 domain.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	McCoy, Margaret E. Finkelman, Fred D. Straus, David B.
Description	Country affiliation: United States Author Affiliation: McCoy ME ( Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA.)
Abstract	T cell activation and effector function is essential for robust immunity. Ag TCR signals are known to regulate T lymphocyte differentiation, but the mechanisms involved in this regulation remain unclear. Recent work has demonstrated that the Src family protein tyrosine kinase p56Lck specifically links TCR signaling to activation of the MAPK pathway through the function of its Src homology 3 (SH3) domain. The MAPK pathway is involved in T cell activation and has previously been implicated in Th2 immunity. We have used Lck SH3 mutant knockin mice (LckW97A) to investigate the potential role of this regulatory mechanism in T lymphocyte activation and effector function. Our results demonstrate that Lck SH3 domain function regulates activation of T lymphocytes as indicated by reduced IL-2 production, CD69 induction, and proliferation of LckW97A T cells following TCR stimulation. Biochemical studies confirm that activation of the MAPK pathway is selectively altered following TCR ligation in LckW97A T lymphocytes. Phospho-ERK induction is reduced, but phospho-phospholipase Cgamma1 induction and calcium mobilization are largely unaffected. Immunization with DNP-keyhole limpet hemocyanin, heat-killed Brucella abortus, or infection with Nippostrongylus brasiliensis demonstrates selectively impaired Th2 immunity with reduced serum levels of IgG1, IgE, and IL-4. In vitro studies show that LckW97A T cells can differentiate into Th2-type cells, but they form IFN-gamma-producing cells under conditions that normally favor Th2 development. These data indicate that the Lck SH3 domain controls T lymphocyte activation by regulating MAPK pathway induction and demonstrate a novel role for Lck in the regulation of Th2-type immunity.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	6
Volume Number	185
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2010-09-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Epitopes, T-lymphocyte Immunology Lymphocyte Specific Protein Tyrosine Kinase P56(lck) Physiology T-lymphocyte Subsets Enzymology Th2 Cells Animals Cell Differentiation Genetics Gene Knock-in Techniques Lymphocyte Activation Chemistry Map Kinase Signaling System Mice Mice, Inbred C57bl Mice, Mutant Strains Nippostrongylus Protein Structure, Tertiary Strongylida Infections Pathology Parasitology Src-family Kinases Comparative Study Research Support, N.i.h., Extramural Research Support, U.s. Gov't, Non-p.h.s. Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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