IL-17-dependent cellular immunity to collagen type V predisposes to obliterative bronchiolitis in human lung transplants.
J Clin Invest
; 117(11): 3498-506, 2007 Nov.
Article
em En
| MEDLINE
| ID: mdl-17965778
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Bronquiolite Obliterante
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Transplante de Pulmão
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Interleucina-17
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Colágeno Tipo V
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Suscetibilidade a Doenças
/
Rejeição de Enxerto
/
Imunidade Celular
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos