Increased immunosuppressive function of CD4(+)CD25(+)Foxp3(+)GITR+ T regulatory cells from NFATc2((-/-)) mice controls allergen-induced experimental asthma.

The expansion of effector T cells is tightly controlled by transcription factors like nuclear factor of activated T cells (NFAT) family members that mediate early intracellular responses to T cell receptor-mediated signals. In this study we show that, after allergen challenge, NFATc2((-/-)) mice had augmented number of functionally intact CD4(+)CD25(++)GITR(++) T regulatory (T regs) cells in the lung. Anti-GITR antibody treatment inhibited T regulatory cell function and enhanced the number of activated lung CD4(+) T cells associated with increased IL-2 and pSTAT-5 in the airways of NFATc2((-/-)) mice in experimental allergic asthma. This agonistic treatment led to increased inflammation in the lung of NFATc2((-/-)) treated mice. These data indicate that NFATc2((-/-)) mice have increased number of CD4(+)CD25(+)Foxp3(+) T regulatory cells with induced immunosuppressive function that control allergen-induced experimental asthma.