title: ICOS-expressing lymphocytes promote resolution of CD8-mediated lung injury in a mouse model of lung rejection.
abstract: Acute rejection, a common complication of lung transplantation, may promote obliterative bronchiolitis leading to graft failure in lung transplant recipients. During acute rejection episodes, CD8(+) T cells can contribute to lung epithelial injury but the mechanisms promoting and controlling CD8-mediated injury in the lung are not well understood. To study the mechanisms regulating CD8(+) T cell-mediated lung rejection, we used a transgenic model in which adoptively transferred ovalbumin (OVA)-specific cytotoxic T lymphocytes (CTL) induce lung injury in mice expressing an ovalbumin transgene in the small airway epithelium of the lungs (CC10-OVA mice). The lung pathology is similar to findings in humans with acute lung transplant. In the presence of an intact immune response the inflammation resolves by day 30. Using CC10-OVA.RAG(-/-) mice, we found that CD4(+) T cells and ICOS(+/+) T cells were required for protection against lethal lung injury, while neutrophil depletion was not protective. In addition, CD4(+)Foxp3 (+) ICOS(+) T cells were enriched in the lungs of animals surviving lung injury and ICOS(+/+) Tregs promoted survival in animals that received ICOS(-/-) T cells. Direct comparison of ICOS(-/-) Tregs to ICOS(+/+) Tregs found defects in vitro but no differences in the ability of ICOS(-/-) Tregs to protect from lethal lung injury. These data suggest that ICOS affects Treg development but is not necessarily required for Treg effector function.
authors: Center for Immunobiology, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors: Qiang
authors: Q
authors: Wu
authors: Gail J
authors: GJ
authors: Gardiner
authors: Elizabeth
authors: E
authors: Berry
authors: Sarah R
authors: SR
authors: Wagner
authors: Tiffany
authors: T
authors: Lu
authors: Bryan S
authors: BS
authors: Clay
authors: Tamson V
authors: TV
authors: Moore
authors: Caroline M
authors: CM
authors: Ferreira
authors: Jesse W
authors: JW
authors: Williams
authors: Andrew D
authors: AD
authors: Luster
authors: Benjamin D
authors: BD
authors: Medoff
authors: Judy L
authors: JL
authors: Cannon
authors: Anne I
authors: AI
authors: Sperling
authors: Rebecca A
authors: RA
authors: Shilling
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D004195:Disease Models, Animal; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology* / Q000401:mortality; D060889:Inducible T-Cell Co-Stimulator Protein / Q000235:genetics* / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D055370:Lung Injury / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D016040:Lung Transplantation / Q000009:adverse effects*; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D009504:Neutrophils; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
chemical_list: D000941:Antigens; D060889:Inducible T-Cell Co-Stimulator Protein; D007376:Interleukin-2; D016753:Interleukin-10
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