IL-17-dependent cellular immunity to collagen type V predisposes to obliterative bronchiolitis in human lung transplants. J Clin Invest 2007 Nov;117(11):3498-506
Date
10/30/2007Pubmed ID
17965778Pubmed Central ID
PMC2040314DOI
10.1172/JCI28031Scopus ID
2-s2.0-36048968753 (requires institutional sign-in at Scopus site) 375 CitationsAbstract
Bronchiolitis obliterans syndrome (BOS), a process of fibro-obliterative occlusion of the small airways in the transplanted lung, is the most common cause of lung transplant failure. We tested the role of cell-mediated immunity to collagen type V [col(V)] in this process. PBMC responses to col(II) and col(V) were monitored prospectively over a 7-year period. PBMCs from lung transplant recipients, but not from healthy controls or col(IV)-reactive Goodpasture's syndrome patients after renal transplant, were frequently col(V) reactive. Col(V)-specific responses were dependent on both CD4+ T cells and monocytes and required both IL-17 and the monokines TNF-alpha and IL-1beta. Strong col(V)-specific responses were associated with substantially increased incidence and severity of BOS. Incidences of acute rejection, HLA-DR mismatched transplants, and induction of HLA-specific antibodies in the transplant recipient were not as strongly associated with a risk of BOS. These data suggest that while alloimmunity initiates lung transplant rejection, de novo autoimmunity mediated by col(V)-specific Th17 cells and monocyte/macrophage accessory cells ultimately causes progressive airway obliteration.
Author List
Burlingham WJ, Love RB, Jankowska-Gan E, Haynes LD, Xu Q, Bobadilla JL, Meyer KC, Hayney MS, Braun RK, Greenspan DS, Gopalakrishnan B, Cai J, Brand DD, Yoshida S, Cummings OW, Wilkes DSMESH terms used to index this publication - Major topics in bold
Antigens, CDBronchiolitis Obliterans
Collagen Type II
Collagen Type V
Disease Susceptibility
Graft Rejection
Humans
Immunity, Cellular
Interferon-gamma
Interleukin-17
Interleukin-1beta
Lung Transplantation
Prospective Studies
Risk Factors
T-Lymphocyte Subsets
T-Lymphocytes, Helper-Inducer
Tumor Necrosis Factor-alpha
