THE CYTOKINE AND HISTOLOGICAL RESPONSE IN ISLET XENOGRAFT REJECTION IS DEPENDENT UPON SPECIES COMBINATION

Background. Islet xenografts have clinical potential, may avoid hypera cute rejection, and therefore are a good place to examine the cellular xenograft immune response. The aim of this study was to examine the c ellular, humoral, and cytokine response in islet xenograft rejection a nd to determine the difference in the immune response with a different donor species. Methods. Two islet xenograft models (DA rat islets to B6AF(1), mouse and canine islets to B6AF(1), mouse) and a mouse syngen eic control model were examined histologically and by a semiquantitati ve polymerase chain reaction method, Results. There was significant up -regulation of all intragraft cytokines tested (interleukin [IL]-2, IL -4, IL-5, IL-10, and interferon-gamma) in both xenograft models compar ed with the controls, However, the dog islet grafts had higher levels of IL-4 and IL-5 gene expression than the rat islet grafts, which, con versely, had higher levels of interferon-gamma gene expression. These differences correlated with the histological and anti-donor antibody p roduction differences between the two models. The dog to mouse model h ad an intense eosinophilic infiltrate and an early up-regulation of an ti-donor antibody, whereas there was little eosinophilic infiltrate an d a delayed anti-donor antibody upregulation in the rat to mouse model , Conclusions, The mouse used different mechanisms to reject the rat a nd canine islets, suggesting that the immune response in islet xenogra ft rejection may be dependent on the species combination, It may not b e possible to characterize the cellular xenograft rejection response i n a bipolar manner as has been the case with humoral rejection respons e, Caution therefore needs to be taken before extrapolating the cellul ar immune responses seen in animal models to the clinical setting.