THE ANALYSIS OF THE MECHANISM OF ALLOGRAFT REJECTION USING KNOCK OUT MICES

小鼠CD4+ T细胞在免疫反应性和异种皮肤移植排斥反应中的重要作用已被报道。为了进一步阐明CD4+和CD8+ T细胞在异种皮肤移植排斥反应中的作用，本研究采用CD4和CD8敲除[C57BL/6 Cr Sic （B6; H-2b）背景]小鼠。将人皮肤移植到CD8敲除小鼠或B6小鼠上，移植后12天内，两种宿主均对人皮肤产生排斥反应。相比之下，CD4敲除小鼠的人皮移植存活时间明显延长[平均存活时间(MST)= 19.3}，标准差（SD）1.6d；Medianl9days]。完全同种异体C3H/He Sic （H-2k）皮肤移植在14天内被CM敲除小鼠排斥，这表明CD4敲除小鼠的非CD4+ T细胞对同种异体移植排斥具有免疫能力。在这些受体小鼠的脾脏中，CD8+ T细胞在人类皮肤移植10天后似乎被激活。免疫组织学分析显示CD4敲除小鼠移植皮肤部位有CD8+ T细胞浸润。为了进一步研究CD8+ T细胞在CD4敲除小鼠中的作用，在第0天进行人皮肤移植，并在第0、5和14天给予抗CD8单克隆抗体（mAb）。给药抗cd8单抗可显著延长人移植皮肤的存活时间。这些结果提示以下两个结论：1)CD4+ T细胞在快速排斥异种人皮移植中起重要作用，2)CD8+ T细胞也能排斥异种人皮移植。

An essential role of murine CD4+ T cells in immune reactivity and skin graft rejection in discordant xenogeneic combinations have been reported. The present study was conducted in order to further clarify the roles of CD4+ and CD8+ T cells in discordant skin xenograft rejection, by using CD4 and CD8 knockout [C57BL/6 Cr Sic (B6 ; H-2b) background] mice. When human skins were grafted on CD8 knockout mice or B6 mice, both hosts rejected human skin grafts within 12 days after grafting. By contrast, survival of human skin grafts was significantly prolonged in CD4 knockout mice [mean survival times (MST)= 19.3 _} standard deviation(SD)1.6days ; Medianl9days]. Fully allogeneic C3H/He Sic (H-2k) skin grafts were rejected within 14 days in CM knockout mice, suggesting that non-CD4+ T cells in CD4 knockout mice were immunocompetent for allograft rejection. In spleens of these recipient mice, CD8+ T cells seemed to be activated 10 days after human skin grafting. Immunohistological analysis revealed the infiltration of CD8+ T cells at the site of transplanted human skin on CD4 knockout mice. In order to further examine the role of CD8+ T cells in CD4 knockout mice, human skin grafting was performed on day 0 followed by administration of anti-CD8 monoclonal antibody (mAb) on days 0, 5, and 14. The administration of anti-CD8 mAb caused the significant prolongation of human skin graft survival. These results indicate the following two conclusions : 1) CD4+ T cells have an essential role in rejecting discordant human skin xenografts rapidly, 2) however, CD8+ T cells also are capable of rejecting discordant human skin xenografts.