SUMMARYHuman lung alveolar epithelial cells constitutively express class II major histocompatibility complex ( MHC). Human lung microvascular endothelial and small airway epithelial cells can be induced to express class II MHC by stimulation with the pro-inflammatory cytokine interferonc. The levels of class II MHC on lung epithelial and endothelial cells were comparable to those seen on an Epstein-Barr virus (EBV )-transformed B-cell line. However, the costimulatory molecules B7-1 and B7-2 were not expressed. The ability of the class II MHC expressing human lung parenchymal cells to present alloantigen to CD4+ T lymphocytes was investigated. Freshly isolated human alveolar epithelial cells (type II pneumocytes) and monolayers of interferon-cstimulated small airway epithelial and lung microvascular endothelial cells were co-cultured with allogeneic CD4+ T lymphocytes and proliferation determined by [3H ]thymidine incorporation. A clear diÂerence was observed between eÂects of the epithelial and endothelial cells on CD4+ T-lymphocyte activation. Alveolar and small airway epithelial cells failed to stimulate the proliferation of allogeneic CD4+ T lymphocytes whereas lung microvascular endothelial cells did stimulate proliferation. This diÂerence could not be explained by the levels of class II MHC or the lack of B7-1 and B7-2 solely. Microvascular endothelial cells, and not alveolar or small airway epithelial cells, possess B7-independent costimulatory pathways.

The development of obliterative bronchiolitis is a common cause for failure of lung allografts. Fibrinogenesis can occur for a number of different reasons but some groups have suggested that cyclosporin A (CsA) and tacrolimus (FK506) have different effects on the cytokines which induce fibrinogenesis. We investigated the effect of tacrolimus and CsA in tissue culture and found that there was indeed a negative effect on human lung small airway epithelial cell proliferation by recombinant transforming growth factor-beta (TGF-beta), which was reversed by anti-TGF-beta. The same effect was seen with CsA at immunosuppressive concentrations, which was also reversed by anti-TGF-beta, whereas no such inhibition was seen with tacrolimus at immunosuppressive doses unless high concentrations were used. Free TGF-beta was confirmed as being elevated in the supernatant of cell culture wells with standard dose CsA as opposed to low dose CsA or tacrolimus using an ELISA assay.

The development of obliterative bronchiolitis is a common cause for failure of lung allo-

Acute allograft rejection is characterized by infiltration of the donor organ by host lymphoid cells, predominantly T lymphocytes. However, the site of proliferation and clonal expansion of alloreactive T lymphocytes is not well defined in man. A group of normal transbronchial biopsies (TBB, n=9) from clinically well lung transplant recipients was compared to TBB showing acute rejection (at least grade A2, n=9), using CD3- and Ki67-specific antibodies to double-label proliferating T lymphocytes. Few double-labeled lymphocytes were present in the normal biopsies (range, 0-3 cells). However, five of the rejection biopsies contained significant numbers of proliferating T lymphocytes (range, 19-47; Fisher's exact test; P=0.029). Furthermore, this positive group contained all three cases of grade A3 rejection in the study, as well as a case with persistent grade A2 rejection on follow-up biopsy. These data demonstrate that T lymphocytes do proliferate in transplanted human lungs; such proliferation is associated with more severe rejection.

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