Evidence of GATA-3-dependent Th2 commitment during the in vivo immune response.
The transcription factor GATA-3 has been shown to play an important role for the in vitro induction of T(h)2 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 T(h)2 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 T(h)2 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.
Tamauchi
Hidekazu
H
Department of Microbiology, Kitasato University School of Medicine, Sagamihara, 228-8555 Kanagawa, Japan.
Terashima
Masazumi
M
Ito
Mamoru
M
Maruyama
Hiroko
H
Ikewaki
Nobunao
N
Inoue
Matsuhisa
M
Gao
Xiuhua
X
Hozumi
Katsuto
K
Habu
Sonoko
S
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology*; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor; D015151:Immunoblotting; D007070:Immunoglobulin A / Q000097:blood; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D018793:Interleukin-13 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells / Q000276:immunology*; D015534:Trans-Activators / Q000276:immunology*
D015704:CD4 Antigens; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D018793:Interleukin-13; D015848:Interleukin-5; D011948:Receptors, Antigen, T-Cell; D015534:Trans-Activators; D007073:Immunoglobulin E; D010047:Ovalbumin