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.

No abstract

We consider situations where a step function with a variable number of steps provides an adequate model for a regression relationship, while the variance of the observations depends on their mean. This model provides for discontinuous jumps at changepoints and for constant means and error variances in between changepoints. The basic statistical problem consists of identification of the number of changepoints, their locations and the levels the function assumes in between. We embed this problem into a quasilikelihood formulation and utilise the minimum deviance criterion to fit the model; for the choice of the number of changepoints, we discuss a modified Schwarz criterion. A dynamic programming algorithm makes the segmentation feasible for sequences of moderate length. The performance of the segmentation method is demonstrated in an application to the segmentation of the Bacteriophage l sequence.

No abstract

Mouse gammadelta T cells produce IL-17 in response to lung injury and are required for an organized inflammatory response and epithelial repair. The lack of gammadelta T cells correlates with increased inflammation and fibrosis.