Wu, QiangGupta, Pawan KumarSuzuki, HidemiWagner, Sarah R.Zhang, ChenCummings, Oscar W.Fan, LinKaplan, Mark H.Wilkes, David S.Shilling, Rebecca A.2015-11-192015-11-192015-07Wu, Q., Gupta, P. K., Suzuki, H., Wagner, S. R., Zhang, C., Cummings, O. W., ... & Shilling, R. A. (2015). CD4 T Cells but Not Th17 Cells Are Required for Mouse Lung Transplant Obliterative Bronchiolitis. American Journal of Transplantation. http://dx.doi.org/10.1111/ajt.13215https://hdl.handle.net/1805/7495Lung 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.en-USPublisher PolicyCD4t-cellslung transplantationArticle