Regulatory T cells dampen pulmonary inflammation and lung injury in an animal model of Pneumocystis pneumonia

CD4(+)CD25(+)FoxP3(+) regulatory T cells are decreased in patients infected with HIV and have been shown to be critical in mediating Ag tolerance in the lung. Because a subset of Pneumocystis-infected individuals develop substantial lung injury, which can be modeled in immune reconstituted scid mice, we used mouse models of Pneumocystis carinii to investigate the role of regulatory T cells in opportunistic infection and immune reconstitution. In this study, we show that CD4(+)CD25(+)FoxP3(+) cells are part of the host response to Pneumocystis in CD4(+) T cell-intact mice. Moreover, lung injury and proinflammatory Th1 and Th2 cytokine levels in the bronchoalveolar lavage fluid and lung homogenate were increased following CD4(+)CD25(-) immune reconstitution in Pneumocystis-infected SCID mice but not in CD4(+)CD25(+) T cell-reconstituted animals. The ability of CD4(+)CD25(+) T cells to control inflammation and injury during the course of Pneumocystis was confirmed by treatment of wild-type C57BL/6 mice with anti-CD25 mAb. These data show that CD4(+)CD25(+) T cells control pulmonary inflammation and lung injury associated with Pneumocystis infection both in the setting of immune reconstitution as well as new acquisition of infection.