International Immunology, Vol. 16, No. 1, pp. 179-187,
January 2004
© 2004 Japanese Society for Immunology
Evidence of GATA-3-dependent Th2 commitment during the in vivo immune response
1 Department of Microbiology, Kitasato University School of Medicine and 4 Department of Pathology, Kitasato University School of Allied Health Science, Sagamihara, 228-8555 Kanagawa, Japan 2 Discovery Research Laboratories II, Sumitomo Pharmaceuticals Co. Ltd, 554-0022 Osaka, Japan 3 Division of Immunology, Central Institute for Experimental Animals, Kawasaki, 216-0001 Kanagawa, Japan 5 Division of Immunology, Kyushu University of Health and Welfare, Faculty of Health and Science, Nobeoka, 882-8508 Miyazaki, Japan 6 Division of Host Defense Mechanism, Department of Immunology, Tokai University School of Medicine, Isehara, 258-1183 Kanagawa, Japan 7 Present address: CUMC Cancer Center, 2500 California Plaza, Omaha, NE 68178, USA
Correspondence to: S. Habu; E-mail: sonoko{at}is.icc.u-tokai.ac.jp
Transmitting editor: K. Okumura
The transcription factor GATA-3 has been shown to play an important role for the in vitro induction of Th2 cells. To clarify how the in vivo immune response is governed under GATA-3 function, we generated double-transgenic mice by crossing GATA-3 transgenic mice with ovalbumin (OVA)-specific TCR transgenic mice. After immunization with OVA, the double-transgenic mice showed increased expression of GATA-3 in antigen-reactive fresh CD4+ T cells, and higher production of IL-5 and IL-13 in cultured spleen cells in the presence of cognate antigen without any polarizing conditions for Th2 cells. Moreover, the immunized double-transgenic mice showed a higher increase of in vivo secretion of IL-5 and IL-13 in bronchoalveolar lavage fluid after OVA aerosol challenging. The serum levels of OVA-specific IgG1, IgE and IgA antibodies were much higher in the immunized double-transgenic mice than TCR transgenic mice. These findings provide direct evidence that antigen-stimulated CD4+ T cells in the immunized mice have already been committed into Th2 cells producing IL-5 and IL-13 selectively through enhanced GATA-3 expression in vivo, thereby inducing higher production of antigen-specific antibody for three isotypes other than IgM.
Keywords: antigen-specific Ig isotype, GATA-3, GATA-3 transgenic mice, ovalbumin-specific TCR transgenic mice, Th2 cytokine
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