The Effect Of Intrathymic Inoculation With Xenogeneic Antigen On The Function Of Macrophage In Pig-to-monkey Model

Introduction: In xenotransplantation, the xenografts are eventually rejected following hyperacute rejection (HAR) by a process collectively referred to as acute humoral xenograft rejection (AHXR) or delayed xenograft rejection (DXR). Macrophage are thought to have important roles in DXR. This study was designed to investigate the influence of intrathymic inoculation with xenogeneic antigen on Fc receptor expression and macrophage phagocytosis of macrophage cells in pig-to-monkey model.Materials and methods: In this experiment, three mixed cell culture were performed using different lymphocytes. The macrophage 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, the Fc receptor expression of macrophage was assayed by colorimetric method of micro-PAP . Phagocytosis of macrophage cells was measured with colorimetric method of neutral red. The mixed lymphocyte reaction (MLR) with H3thymidine performed to assess the cytotoxicity of T cells.The level of IL-10 and TNF in supernatant were inspected by ELISA. Results: Compared with the result before intrathymic inoculation, the Fc receptor expression and macrophage phagocytosis of macrophage cells hasno change after the intrathymic treatment(P>0.05), and the secretion of IL-10 and TNF-a also remain stable. But the cytotoxicity of T cells was suppressed significantly(P<0.05) in recipients after intrathymic inoculation with xenogeneic antigens. The level of TNF-a was dropped from 51.2 3.0 U/ml to 39.3+2.7 U/ml (P<0.05)and the level IL-10 of increased from 0.82+0.13 U/ml to 2.60+0.57 U/ml (P<0.05) after pretreament. After mixed with T cells, the Fc receptor expression and macrophage phagocytosis of Macrophage cells were respectively increased from 0.378 +0.044 to 0.612 + 0.042 (PO.05) and from 0.178+0.014 to 0.312 + 0.019 (PO.05), but the suppression of T cells function could not reduce Fc receptor expression and macrophage phagocytosis of Macrophage cells(P > 0.05). Conclusions: Intrathymic inoculation of xenogeneic antigen can not influence the function of Macrophage cells and has no effect on the cytokine secretion of Macrophage cells. This pretreament can specially suppress the cytotoxicity of T cells, decrease the level of TNF-a and increase IL-10 of cytokines secreted by T cells in recipient. T cells can enhance the function of Macrophage cells, but has not inhabit the function of Macrophage cells if the function of T cells was suppressed.