Allograft acceptance despite differential strain-specific induction of TGF-β/IL-10-mediated immunoregulation
Allograft acceptance despite differential strain-specific induction of TGF-β/IL-10-mediated immunoregulation
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DOI：
10.1034/j.1600-6143.2002.20903.x
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发表时间：
2002-10-01
影响因子：
8.8
通讯作者：
Orosz, CG
中科院分区：
文献类型：
--
作者：
Bickerstaff, AA;Wang, JJ;Orosz, CG
我们检测了C57BI/6和BALB/c小鼠接受同种异体心脏移植时的免疫途径。C57BI/6小鼠接受硝酸镓（GN）或抗cd40l单抗（MR1）处理的DBA/2同种异体心脏移植物。这些同种异体移植受体小鼠不能产生供体反应性延迟型超敏反应（DTH），并发展出供体诱导的抑制DTH反应的免疫调节机制。相比之下，BALB/c小鼠在MR1而非GN处理下接受C57BI/6同种异体心脏移植。这些同种异体移植物受体小鼠表现出适度的供体反应性DTH反应，并且不发展供体诱导的DTH反应的免疫调节。对排斥移植物组织的实时PCR分析显示，在细胞因子mrna的产生中没有菌株相关的倾斜。在相关研究中，C57BI/6受体接受细胞因子和同种异体抗原培养的同基因腹膜渗出细胞（PECs）不能对同种异体抗原产生DTH反应，除非在DTH部位存在转化生长因子- β (tgf - β)的中和抗体，显示细胞介导的同种异体免疫反应的调节。相比之下，接受细胞因子和同种异体抗原教育的PECs的BALB/c受体对同种异体抗原表达强烈的DTH反应，表明缺乏调节的同种异体免疫。综上所述，C57BI/6小鼠通过接受同种异体心脏移植和产生tgf - β相关的供体反应性T细胞反应来响应免疫抑制，而BALB/c小鼠不产生这些调节反应，但仍然可以接受同种异体心脏移植。
We examined the immune approaches that C57BI/6 and BALB/c mice take when treated to accept cardiac allografts. C57BI/6 mice accept DBA/2 cardiac allografts when treated with gallium nitrate (GN) or anti-CD40L mAb (MR1). These allograft acceptor mice fail to mount donor-reactive delayed type hypersensitivity (DTH) responses, and develop a donor-induced immunoregulatory mechanism that inhibits DTH responses. In contrast, BALB/c mice accept C57BI/6 cardiac allografts when treated with MR1 but not with GN. These allograft acceptor mice display modest donor-reactive DTH responses, and do not develop donor-induced immune regulation of DTH responses. Real-time PCR analysis of rejecting graft tissues demonstrated no strain-related skewing in the production of cytokines mRNAs. In related studies, C57BI/6 recipients of cytokine and alloantigen educated syngeneic peritoneal exudate cells (PECs) failed to mount DTH responses to the alloantigens unless neutralizing antibodies to transforming growth factor-beta (TGF-beta were present at the DTH site demonstrating regulation of cell-mediated alloimmune responses. In contrast, BALB/c recipients of cytokine-and alloantigen-educated PECs expressed strong DTH responses to alloantigens demonstrating a lack of regulated alloimmunity. In conclusion, C57BI/6 mice respond to immunosuppression by accepting cardiac allografts and generating TGF-beta-related regulation of donor-reactive T cell responses, unlike BALB/c mice that do not generate these regulatory responses yet still can accept cardiac allografts.