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* Center for Molecular Immunology and Infectious Disease and Department of Veterinary and Biomedical Sciences and
Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802;
National Human Genome Research Institute,
National Institute of Allergy and Infectious Disease, and
¶ National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892; and
|| Department of Environmental Health Sciences, Johns Hopkins University, Baltimore, MD 21205
Itk and Txk/Rlk are Tec family kinases expressed in T cells. Itk is expressed in both Th1 and Th2 cells. By contrast, Txk is preferentially expressed in Th1 cells. Although Itk is required for Th2 responses in vivo and Txk is suggested to regulate IFN-
expression and Th1 responses, it remains unclear whether these kinases have distinct roles in Th cell differentiation/function. We demonstrate here that Txk-null CD4+ T cells are capable of producing both Th1 and Th2 cytokines similar to those produced by wild-type CD4+ T cells. To further examine whether Itk and Txk play distinct roles in Th cell differentiation and function, we examined Itk-null mice carrying a transgene that expresses Txk at levels similar to the expression of Itk in Th2 cells. Using two Th2 model systems, allergic asthma and schistosome egg-induced lung granulomas, we found that the Txk transgene rescued Th2 cytokine production and all Th2 symptoms without notable enhancement of IFN- expression. These results suggest that Txk is not a specific regulator of Th1 responses. Importantly, they suggest that Itk and Txk exert their effects on Th cell differentiation/function at the level of expression.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grants AI051626 and AI065566, the American Health Association (to A.A.), and by the intramural program of the National Institutes of Health, National Human Genome Research Institute (to A.M.V., J.C., J.G.-R., and P.L.S.), the National Institute of Allergy and Infectious Disease (to D.J. and A.S.), and the National Institute of Child Health and Human Development (to C.S. and P.L.). N.S. thanks the American Academy of Allergy, Asthma and Immunology’s Strategic Training in Allergy Research (ST*AR) Award for support.
2 N.S. and A.M.V. contributed equally to this work.
3 P.L.S. and A.A. are to be considered co-senior authors.
4 Address correspondence and reprint requests to Dr. Avery August, Pennsylvania State University, Center for Molecular Immunology and Infectious Disease, 115 Henning Building, University Park, PA 16802 or Dr. Pamela L. Schwartzberg, 4A38, 49 Convent Drive, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892. E-mail addresses: avery{at}psu.edu and pams{at}mail.nih.gov
5 Abbreviations used in this paper: PH, pleckstrin homology; AHR, airway hyperresponsiveness; BAL, bronchoalveolar lavage; qRT-PCR, quantitative real-time PCR; SEA, schistosome egg Ag; WT, wild type.
6 The online version of this article contains supplemental material.
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