Lung allograft rejection in the rat. III. Corresponding morphological rejection phases in various rat strain combinations.

Rejection of RT1-incompatible lung grafts has been found in the study reported in our accompanying article to result in four consecutive morphological rejection phases: the latent, the vascular, the alveolar, and the destruction phase. The most prominent signs of rejection, however, occur early in the vascular phase in the bronchus-associated lymphoid tissue (BALT) of these grafts. In this study we investigated whether these four phases and the early rejection signs in BALT are universal phenomena of lung allograft rejection. Therefore, various donor-recipient combinations of inbred rat strains, incompatible for the MHC or for minor loci, were compared with respect to histological rejection phenomena--both in the lung graft and in the recipient's spleen--and alloantibody formation. The four rejection phases appeared sequentially in grafts of all combinations. Duration of the phases depended on the degree of histoincompatibility of the graft. Again, BALT was involved early in the rejection process. During the vascular phase a strong immune response developed in the spleen, and in the alveolar phase antibodies circulated in the blood. We conclude that these morphological rejection phases are universal phenomena of the rejection process against lung allografts in rats. Corresponding phenomena have been described for other species, even in immunosuppressed recipients. Based on these data, a new concept of the universal rejection process of lung allografts is postulated.