CD4(+)CD25(+) regulatory T cells attenuate Hypersensitivity Pneumonitis by suppressing IFN-gamma production by CD4(+) and CD8(+) T cells.

HP results from the repeated inhalation of environmental antigens; however, the roles of CD4(+)CD25(+) T(reg) cells in HP are unknown. Therefore, we investigated the functions of CD4(+)CD25(+) T(reg) cells in SR-induced murine HP. More severe HP was observed in CD4(+)CD25(+) T(reg) cell-depleted mice than in control mice in terms of histological alterations, inflammatory cell numbers in BALF, and the serum level of SR-specific IgG, which were restored by the adoptive transfer of CD4(+)CD25(+) T(reg) cells. The CD4(+)CD25(+) T(reg) cell-depleted mice also showed elevated levels of IFN-gamma, TGF-beta, and reduced IL-4 production in the lungs. Moreover, IL-10 production of CD4(+)CD25(+) T(reg) cells and direct contact between CD4(+)CD25(+) T(reg) cells and CD4(+) or CD8(+) T cells in BALF resulted in reduced IFN-gamma production. Taken together, CD4(+)CD25(+) T(reg) cells play a protective role in SR-induced HP by suppressing IFN-gamma production by T cells.