Dendritic cells and macrophages in lung allografts a role in chronic rejection?

Antigen presentation by lung macrophages/dendritic cells (DC) is thought to be important in obliterative bronchiolitis/bronchiolitis obliterans syndro me (OB/BOS), which severely limits survival post-lung transplantation. Howe ver, a recent study found minimal numbers of DC in lung allografts. We look ed at numbers and phenotype of macrophages/DC in lung allografts using endo bronchial biopsy (EBB) and transbronchial biopsy (TBB) from 22 lung transpl ant patients. Biopsies were stained with monoclonal markers of DC (CD1a, RF D1, and major histocompatibility complex [MHC] Class II), and "suppressor m acrophages" (RFD1 and RFD7). Dendritic cells were also stained for the cost imulatory molecules CD80 and CD86. Significantly greater numbers of DC/high -power field (HPF) were seen in biopsies when we defined DC using dendritic morphology and Class II MHC expression instead of CD1a expression. Dendrit ic cell numbers were significantly higher in eight patients with OB/BOS com pared with 14 stable patients. Fifty percent of DC expressed CD86 and 20% e xpressed CD80. There was no difference in CD80 or CD86 expression between O B/BOS patients and stable patients. There was no correlation between DC num bers and presence or absence of acute rejection (AR), and/or cytomegaloviru s (CMV) pneumonitis on current or prior biopsies. There were significantly more MHC Class II DC in EBB compared with TBB. We found minimal staining fo r lung macrophages capable of suppressing T-cell inflammation. We conclude that studies of lung allografts may underestimate DC numbers if relying on CD1a as the sole marker of DC. DC are increased in patients with OB/BOS com pared with stable patients. EBB may be more important than TBB in looking f or inflammatory changes of OB. DC expressing costimulatory molecules are pr esent in lung allografts, and costimulatory pathway blockade may be useful in human lung allografts. Also, the absence of "suppressor" macrophages may increase susceptibility of human lung allografts to the rejection process.