CD4 T Cells but Not Th17 Cells Are Required for Mouse Lung Transplant Obliterative Bronchiolitis |
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| Authors: | H. Suzuki S. R. Wagner C. Zhang O. W. Cummings L. Fan M. H. Kaplan D. S. Wilkes R. A. Shilling |
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| Affiliation: | 1. Pulmonary and Critical Care Medicine and Center for Immunobiology, Departments of Medicine and Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN;2. Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine and Department of Microbiology and Immunology, University of Illinois at Chicago, College of Medicine, Chicago, IL;3. Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN;4. Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN |
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| Abstract: | Lung transplant survival is limited by obliterative bronchiolitis (OB), but the mechanisms of OB development are unknown. Previous studies in a mouse model of orthotopic lung transplantation suggested a requirement for IL‐17. We have used this orthotopic mouse model to investigate the source of IL‐17A and the requirement for T cells producing IL‐17A. The major sources of IL‐17A were CD4+ T cells and γδ T cells. Depletion of CD4+ T cells led to a significantly decreased frequency and number of IL‐17A+ lymphocytes and was sufficient to prevent acute rejection and OB. However, mice with STAT3‐deficient T cells, which are unable to differentiate into Th17 cells, rejected lung allografts and developed OB similar to control mice. The frequency of IL‐17A+ cells was not decreased in mice with STAT3‐deficient T cells due mainly to the presence of IL‐17A+ γδ T cells. Deficiency of γδ T cells also did not affect the development of airway fibrosis. Our data suggest that CD4+ T cells are required for OB development and expansion of IL‐17A responses in the lung, while Th17 and γδ T cells are not absolutely required and may compensate for each other. |
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| Keywords: | basic (laboratory) research/science immunobiology lung transplantation/pulmonology animal models: murine lung (allograft) function/dysfunction T cell biology bronchiolitis obliterans (BOS) |
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