TY - JOUR
T1 - Regulatory T cells dampen pulmonary inflammation and lung injury in an animal model of Pneumocystis pneumonia
AU - McKinley, Laura
AU - Logar, Alison J.
AU - McAllister, Florencia
AU - Zheng, Mingquan
AU - Steele, Chad
AU - Kolls, Jay K.
PY - 2006/11/1
Y1 - 2006/11/1
N2 - CB4+CB25+FoxP3+ regulatory T cells are decreased in patients infected with HW 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.
AB - CB4+CB25+FoxP3+ regulatory T cells are decreased in patients infected with HW 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.
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U2 - 10.4049/jimmunol.177.9.6215
DO - 10.4049/jimmunol.177.9.6215
M3 - Article
C2 - 17056551
AN - SCOPUS:33750335078
SN - 0022-1767
VL - 177
SP - 6215
EP - 6226
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -