EXPRESSION OF CLASS II MAJOR HISTOCOMPATIBILITY COMPLEX ANTIGENS BY BRONCHIAL EPITHELIUM IN RAT LUNG ALLOGRAFTS

Abstract

Variation in expression of class II major histocompatibility complex antigens on bronchial epithelial cells and vascular endothelium were investigated in normal rat lungs and allografted lungs during acute rejection and after cyclosporine (CsA) treatment. BN (RT1n) left lungs were transplanted into LEW (RT1i) recipients. Lungs were excised during acute rejection in untreated rats on postoperative days 1 through 5, and after CsA treatment (25 mg/kg on days 2 and 3) on days 5 and 100. Cryostat sections were examined for class II antigen expression with an immunoperoxidase technique, using various monoclonal antibodies. In the normal lung, class II antigens were not expressed by epithelial or endothelial cells. In the allografts, induction of class II antigens closely correlated with the rejection process: on day 2, the ciliated bronchial epithelium was locally positive; it became uniformly positive with increasing cellular peribronchial infiltration on days 3 and 4. CsA treatment prevented class II antigen expression to a certain extent, leaving the bronchial epithelium weakly positive at 100 days. Endothelial cells were invariably negative for class II antigens in all allografted lungs. The class II antigens expressed on the bronchial epithelial cells were of graft origin, except for recipient-type class II molecules found on the ciliated surface in CsA-treated animals. We conclude that expression of class II antigens by bronchial epithelium is the result of a bronchus-directed rejection process, and hypothesize that such a rejection process may have caused bronchiolitis obliterans in several of the patients with combined heart-lung transplants. Important is the observation that class II molecules can be present on the membranes of cells that do not themselves produce these antigens.