The IL-4 production capability of different strains of naive CD4+ T cells controls the direction of the Th cell response

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Abstract
The qualitative nature of an immune response raised against infectious pathogens depends upon the phenotypes of Th cell subsets, which secrete distinct types of cytokines. Genetic background is known to greatly influence the nature of the Th cell response. However, the precise nature of this influence still remains unclear. In the present study, we demonstrate that CD62L+, CD44low and CD4+ naive T cells from BALB/c mice are capable of producing significant amounts of IL-4, while naive T cells from B10.D2 mice exhibit no IL-4 production. The addition of exogenous IL-4 into the B10.D2 induction culture recovered Th2 development, thereby indicating that the potential of naive T cells to secrete IL-4 at primary activation is likely to substantially influence development of Th2. Regulation of the IL-4 gene in naive T cells differs from that in cells committed towards becoming Th2 cells, based on the observation that naive T cells from STAT6-deficient mice having a BALB/c background produce detectable amounts of IL-4. The IL-4 promoter region was found to be equally histone acetylated in both BALB/c and B10.D2 naive T cells by primary TCR activation. Interestingly, the expression levels of transcription factors NF-AT and GATA-3, which regulate promoter activity, differ between BALB/c and B10.D2 cells. These results suggest that the differences in expression level between the two transcriptional factors may affect the potential of naive T cells to secrete IL-4, which may subsequently influence the development of Th cell phenotypes.