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.
McKinley
Laura
L
Department of Pediatrics, and Division of Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, 3705 Fifth Avenue, Pittsburgh, PA 15213, USA.
Logar
Alison J
AJ
McAllister
Florencia
F
Zheng
Mingquan
M
Steele
Chad
C
Kolls
Jay K
JK
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D015704:CD4 Antigens / Q000032:analysis; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000032:analysis; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis / Q000037:antagonists & inhibitors; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011020:Pneumonia, Pneumocystis / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000906:Antibodies; D015704:CD4 Antigens; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit