Anti-tubular basement membrane antibodies and giant cell formation in a model of chronic renal allograft rejection

Background. In the Fisher (F344)-to-Lewis (LEW) kidney transplantation (Tx) model of chronic rejection, antibodies reactive with tubular basement membranes have been found. We investigated whether giant cells, typical for a granulomatous inflammatory reaction, can be found during allograft rejection. Methods. F344-to-LEW renal Txs were performed, and kidneys were removed at various time points. Kidneys were analyzed by histology and immunohistochemistry. Interferon-gamma levels were measured by reverse-transcriptase polymerase chain reaction. Results. Multinucleated Langhans'-type giant cells were found in F344 allografts at days 21 and 30 and disappeared thereafter. Giant cells were not observed in LEW allografts. The giant cells were ED1, OX-43, and major histocompatibility complex class 11 positive. All grafts showed transient expression of interferon-gamma, peaking at days 7 to 14 post-Tx. Conclusion. Granulomatous inflammation with giant cell formation occurs in the F344-to-LEW model and may represent an alloimmune response against tissue-specific antigens.