The Study On The Influence Of Intrathymic Inoculation With Xenogeneic Antigen On The Function Of Lymphocyte

Department of Cardiovascular Surgery and Laboratory of Organ Transplantation, the First Affiliated Hospital of Soochow UniversityIntroduction: In xenotransplantation, the xenografts are eventually rejected by a process collectively referred to as hyper acute xenograft rejection (HAR) or delayed xenograft rejection (DXR). Natural killer cells and T cells are thought to have important roles in DXR This study was designed to investigate the influence of intrathymic inoculation with xenogeneic antigen on the function of recipient lymphocyte, especially natural killer (NK) cells, in pig-to-monkey xenotransplantation model.Materials and methods: In this experiment three mixed cell cultures were performed using different lymphocytes. The NK cells and T cells from recipients(Rhesus monkey) were, respectively, mixed cultured with lymphocyte from donors(meishan pig) before intrathymic pretreatment. The same mixed culture were performed using lymphocyte from recipient after the intrathymic inoculation of donor xenogeneic antigen. After incubation, cells were washed and a 3H-TdR releasing assay was performed to assess the cytotoxicity of natural killer cells and T cells. The level of IFN- Y and TNF-a in supernatant were assayed by ELISA.Results: Compared with the result before inoculation, the cytotoxicity of NK cells has no change after the intrathymic treatment(P > 0.05), and the secretion of IFN- Y and TNF- a also remain stable. But the cytotoxicity of Tcells was significantly suppressed (P<0.05). The level of IFN- Y secreted by T cells was dropped from 93.9 7.2pg/ml to 79.9 5.8pg/ml(P<0.05)and the level of TNF- a was obviously dropped from 19.6 1.9U/ml to 13 2 2.6U/ml(P<0.05). After incubation with T cells, the cytotoxicity of NK cells was improved from 44.4 5.2% to 57.1 6.3%(P < 0.05), but the suppression of T cell function can not reduced the cytotoxicity of natural killer cells(P> 0.05).Conclusions: Intrathymic inoculation of xenogeneic antigen can specially suppress the cytotoxicity of T cells and decrease the level of cytokines secreted by T cells in recipient. But this kind of intrathymic pretreatment can not influence the cytotoxicity of NK cells and has no effect on the cytokine secretion of NK cells. Then T cells can enhance the cytotoxicity of NK cells through cytokines, but can not decrease the cytotoxicity of NK cells if the function of T cells was suppressed. There may be the immune signal transduction between NK cells and T cells.