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 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.