Resolution of airway inflammation and hyperreactivity after in vivo transfer of CD4+ CD25+ regulatory T cells is interleukin 10 dependent

Deficient suppression of T cell responses to allergen by CD4(+) CD25(+) regulatory T cells has been observed in patients with allergic disease. Our current experiments used a mouse model of airway inflammation to examine the suppressive activity of allergen- specific CD4(+) CD25(+) T cells in vivo. Transfer of ovalbumin ( OVA) peptide - specific CD4(+) CD25(+) T cells to OVA-sensitized mice reduced airway hyperreactivity ( AHR), recruitment of eosinophils, and T helper type 2 ( Th2) cytokine expression in the lung after allergen challenge. This suppression was dependent on interleukin ( IL) 10 because increased lung expression of IL- 10 was detected after transfer of CD4(+) CD25(+) T cells, and regulation was reversed by anti - IL- 10R antibody. However, suppression of AHR, airway inflammation, and increased expression of IL- 10 were still observed when CD4(+) CD25(+) T cells from IL- 10 gene - deficient mice were transferred. Intracellular cytokine staining confirmed that transfer of CD4(+) CD25(+) T cells induced IL- 10 expression in recipient CD4(+) T cells, but no increase in IL- 10 expression was detected in airway macrophages, dendritic cells, or B cells. These data suggest that CD4(+) CD25(+) T cells can suppress the Th2 cell - driven response to allergen in vivo by an IL- 10 - dependent mechanism but that IL- 10 production by the regulatory T cells themselves is not required for such suppression.