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CD4 T Cells but Not Th17 Cells Are Required for Mouse Lung Transplant Obliterative Bronchiolitis
Author(s) -
Wu Q.,
Gupta P. K.,
Suzuki H.,
Wagner S. R.,
Zhang C.,
Cummings O. W.,
Fan L.,
Kaplan M. H.,
Wilkes D. S.,
Shilling R. A.
Publication year - 2015
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.13215
Subject(s) - medicine , interleukin 17 , lung , lung transplantation , bronchiolitis , immunology , fibrosis , transplantation , immune system , pathology , virus
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.