Activation of Complement in the Discordant Heart Xenotransplantation of Pig-to-Monkey Model and the Impact of Intrathymic Inoculation of Xenogeneic Antigen Combined With Whole-Body γ-Radiation

Abstract

Objective This study investigated changes in complement in discordant heart xenotransplantation using a pig-to-monkey model as well as the impact of intrathymic inoculation (IT) with xenogeneic antigen combined with whole-body γ-radiation (WBI). Methods In this experiment, pigs and monkeys selected as donors and recipients, respectively, were randomly divided into three groups: a blank group (group A), a whole-body irradiation group (group B) and an irradiation plus intrathymic injection group (group C). In every group, monkeys underwent heterotopic heart xenotransplantation. Results The results showed that the survival of donor hearts in group C was significantly longer than that of group A ( P < .01). In mixed lymphocyte reactions, there was a significant reduction of the stimulation index in group C compared with group A. After xenotransplantation, the level of xenoreactive antibody in group C rose slower than that in group A or group B ( P < .01). After rejection, the levels of CD46 and C3 declined greatly. Conclusions These results suggested that pretreatment with IT and WBI induced T-cell immunosuppression, restraining elicited xenoreactive antibody production of both immunoglobulin M and immunoglobulin G classes. However, it did not hinder complement activation via the classical pathway during hyperacute rejection and consequent xenograft rejection.