CD4 T Cells but Not Th17 Cells Are Required for Mouse Lung Transplant Obliterative Bronchiolitis

• DOI: 10.1111/ajt.13215
• Publication Date: 2015-03-13T20:35:00Z
• Authors: Q. Wu; P.K. Gupta; H. Suzuki; S.R. Wagner; C. Zhang; O.W. Cummings; L. Fan; M.H. Kaplan; D.S. Wilkes; R.A. Shilling
• Keywords: CD4-Positive T-Lymphocytes; Mice, Knockout; STAT3 Transcription Factor; 0301 basic medicine; Graft Survival; Interleukin-17; Flow Cytometry; CD4; Lymphocyte Depletion; 3. Good health; Mice, Inbred C57BL; Disease Models, Animal; Interferon-gamma; Mice; 03 medical and health sciences; lung transplantation; Animals; Th17 Cells; Bronchiolitis Obliterans; t-cells; Lung Transplantation

Lung transplant survival is limited by obliterative bronchiolitis (OB), but the mechanisms of OB development are unknown. Previous studies in a mouse model orthotopic lung transplantation suggested requirement for IL-17. We have used this to investigate source IL-17A and T cells producing IL-17A. The major sources were CD4(+) γδ cells. Depletion led significantly decreased frequency number IL-17A(+) lymphocytes was sufficient prevent acute rejection OB. However, mice with STAT3-deficient cells, which unable differentiate into Th17 rejected allografts developed similar control mice. not due mainly presence Deficiency also did affect airway fibrosis. Our data suggest that required expansion responses lung, while absolutely may compensate each other.