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.