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

基因敲除小鼠同种异体移植排斥机制分析

基本信息

批准号：
09671384
负责人：
TOMITA Yukihiro
金额：
$ 2.24万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671384/
关键词：
CD4+ T cells CD4 and CD8 knockout mice xenografts discordant skin graft 抗原認識 CD4 CD8

项目摘要

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.

已经报道了鼠CD 4 + T细胞在不一致异种组合中的免疫反应性和皮肤移植物排斥中的重要作用。本研究采用CD 4和CD 8基因敲除[C57 BL/6 Cr Sic（B6 ; H-2b）背景]小鼠，进一步阐明CD 4+和CD 8 + T细胞在异种皮肤移植排斥反应中的作用。当人类皮肤移植到CD 8基因敲除小鼠或B6小鼠上时，两种宿主都在移植后12天内排斥人类皮肤移植物。相比之下，人皮肤移植物在CD 4基因敲除小鼠中的存活时间显著延长[平均存活时间（MST）= 19.3 _，标准差（SD）1.6天;中位数19天]。完全同种异体C3 H/He Sic（H-2k）皮肤移植物在CM敲除小鼠中在14天内被排斥，表明CD 4敲除小鼠中的非CD 4 + T细胞对同种异体移植物排斥具有免疫活性。在这些受体小鼠的脾脏中，CD 8 + T细胞似乎在人皮肤移植后10天被激活。免疫组织化学分析显示，在CD 4基因敲除小鼠的移植人皮肤部位，CD 8 + T细胞浸润。为了进一步检查CD 8 + T细胞在CD 4敲除小鼠中的作用，在第0天进行人皮肤移植，然后在第0、5和14天施用抗CD 8单克隆抗体（mAb）。抗CD 8单克隆抗体的施用引起人皮肤移植物存活的显著延长。这些结果表明以下两个结论：1）CD 4 + T细胞在快速排斥不协调的人皮肤异种移植物中具有重要作用，2）然而，CD 8 + T细胞也能够排斥不协调的人皮肤异种移植物。