Limited immune diversity in urodela: chronic transplantation responses occur even with family-disparate xenografts.

Urodele amphibians are thought to have poorer immune responses than evolutionary more ancestral vertebrate classes, such as bony fish. We investigated skin graft rejection and transplantation immunity in Urodele amphibians, Japanese newts, and Asiatic salamanders, and compared these findings to those from transplants in several species of frogs. The skin grafts used in this study were either allogeneic or xenogeneic. The mean survival time of the first set of allografts at 20°C was approximately 60 days for chronic responses in Urodela and 20 days for acute responses in Anura. As the graft survival times of urodeles were significantly longer than those of anurans, even when urodeles were repeatedly grafted from identical donors, there appear to be substantial differences in transplantation immunity between Urodela and Anura. These slow responses in Urodela may not be accompanied by the expansion of cytotoxic T cells, as observed in fish and anuran species, which are known to have functional major histocompatibility complex (MHC)-class I systems. In our study, approximately five histo-incompatible immunogenic components were found to be involved in chronic responses in newts. Similar chronic responses were also observed in xenograft rejection in newts. In contrast, xenografts were rejected in frogs due to an accelerated acute response, possibly involving natural killer cells. Our findings that some anti-allogeneic components appear to be shared with xenogeneic components indicate that the diversification of the acquired immune system is poorly developed in Urodela.

Chronic transplantation immunity in newts: temperature susceptibility of an effector phase in allo-skin graft rejection.

Urodele amphibians are unique due to their greatly reduced immune responsiveness compared to bony fishes, which show acute immune responsiveness. In newts, the mean survival time of allogenic skin grafts in the transplantation immunity was 48.8 ± 8.3 days at 25°C, suggesting that it occurs in a chronic manner. The graft rejection process was categorized into three stages: a latent stage with frequent blood circulation, or the immune induction phase; a vascular stoppage stage with dominant infiltrating cells of T cells; and a rejection stage showing the change of the dominant cells to monocytes/macrophages, probably as effector cells, tetntatively referred to as the immune effector phase. The immune induction phase is susceptible to the cyclophosphamide (CY) mitosis inhibitor, but not to a temperature shift from 18 to 27°C, while the immune effector phase is susceptible to temperature shifts, but not CY-treatment, although the temperature shift failed to shorten the graft survival time to less than 25 days, which nearly equals that of the secondary set of grafts where the lack of complete blood circulation is remarkable and graft rejection is resistant to CY-treatment. In contrast, a very low temperature (5-10°C) completely prevented effector generation in newts; in frogs, however, it is reported that such low temperatures did not prevent the generation of effectors. Taken together, these data suggest that chronic responses in newts are due to effector cells other than cytotoxic T cells; possible effector cells are discussed.