THE ROLE OF INDIRECT RECOGNITION IN INITIATING REJECTION OF SKIN-GRAFTS FROM MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II-DEFICIENT MICE
THE ROLE OF INDIRECT RECOGNITION IN INITIATING REJECTION OF SKIN-GRAFTS FROM MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II-DEFICIENT MICE
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DOI：
10.1073/pnas.90.8.3373
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发表时间：
1993-04-15
影响因子：
11.1
通讯作者：
GLIMCHER, LH
中科院分区：
文献类型：
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作者：
AUCHINCLOSS, H;LEE, R;GLIMCHER, LH
体外研究已经揭示了T细胞可以对同种异体抗原应答的几种途径，包括对同种异体II类抗原的CD4+直接应答，对同种异体I类抗原的CD8+直接应答，以及对与应答者II类分子相关的同种异体抗原的肽的CD4+“间接"应答。然而，到目前为止，皮肤移植排斥反应的体内研究仅提供了两种直接途径的贡献而不是间接识别的明确证据。我们使用主要组织相容性复合物II类缺陷小鼠作为供体，以测试皮肤移植物排斥反应中间接识别的作用。II类缺陷的皮肤总是被正常的受体毫不拖延地拒绝。去除受体CD8+细胞（使动物依赖于CD4+功能）或耗尽受体CD4+细胞表明，CD4+细胞通常参与，有时绝对需要在这种快速排斥反应。由于供体移植物缺乏II类抗原，因此CD4+细胞必须具有与受体II类分子结合的识别供体抗原。因此，这些结果表明，间接识别可以启动快速皮肤移植排斥反应。
In vitro studies have revealed several pathways by which T cells can respond to alloantigens, including CD4+ direct responses to allogeneic class II antigens, CD8+ direct responses to allogeneic class I antigens, and CD4+ ''indirect'' responses to peptides of alloantigens presented in association with responder class II molecules. In vivo studies of skin graft rejection, however, have so far provided clear evidence for the contribution of only the two direct pathways and not for indirect recognition. We have used major histocompatibility complex class II-deficient mice as donors to test the role of indirect recognition in rejection of skin grafts. Class II-deficient skin was always rejected without delay by normal recipients. Removal of recipient CD8+ cells (to leave the animals dependent on CD4+ function) or depletion of recipient CD4+ cells revealed that CD4+ cells were usually involved and sometimes absolutely required in this rapid rejection. Since the donor grafts lacked class II antigens, the CD4+ cells must have recognized donor antigens presented in association with recipient class II molecules. These results therefore indicate that indirect recognition can initiate rapid skin graft rejection.