Induction of endotoxin tolerance inhibits alloimmune responses
Induction of endotoxin tolerance inhibits alloimmune responses
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DOI：
10.1016/j.trim.2006.06.002
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发表时间：
2006-11-01
影响因子：
1.5
通讯作者：
Asahara, Toshimasa
中科院分区：
文献类型：
--
作者：
Ishiyama, Kohel;Ohdan, Hideki;Asahara, Toshimasa
最近有报道称，内毒素耐受(ET)的诱导抑制了主要组织相容性复合体(MHC)限制性的抗原提呈。内毒素耐受的定义是在第一次遇到内毒素(LPS)后对内毒素(LPS)攻击的反应减弱。这提出了一个问题，即是否可以通过在移植供者中诱导ET来抑制同种免疫反应。C57BL/6小鼠在攻击前给予低剂量的内毒素，然后用大剂量的内毒素诱导ET。将内毒素耐受的C57BL/6小鼠的心脏移植到BALB/c小鼠体内。内毒素耐受的同种异体心脏移植物存活时间明显延长。用C57BL/6小鼠照射后的脾细胞和BALB/c小鼠的同种异体脾细胞进行混合淋巴细胞反应(NILR)试验。MLR试验采用CFSE，结果显示，内毒素耐受小鼠的脾细胞不能诱导同种异体CD4(+)和CD8(+)T细胞的增殖。使用内毒素耐受刺激物对MLR培养上清液进行细胞因子分析，发现Th1/Th2平衡明显向Th2型反应转变。ET的诱导增加了髓系树突状细胞(DC)表达抗原提呈所需分子的比例，有利于Th2应答的发展，但降低了淋巴相关DC表达这些分子的比例，有利于Th1应答的发展。虽然这些发现与内毒素耐受同种异体心脏移植物延长存活时间的相关性仍有待阐明，但这是第一个证明在供体动物体内诱导ET抑制同种免疫反应的研究。(C)2006爱思唯尔B.V.保留所有权利。
It was recently reported that the induction of endotoxin tolerance (ET), which is defined as a reduced response to a lipopolysaccharide (LPS) challenge following the first LPS encounter, inhibits major histocompatibility complex (MHC)-restricted antigen presentation. This raises the question whether alloimmune responses can be inhibited by inducing ET in transplant donors. C57BL/6 mice were treated with a low dose of LPS prior to a challenge with a high dose of LPS to induce ET. Hearts from endotoxin-tolerized C57BL/6 mice were transplanted to BALB/c mice. The survival of the endotoxin-tolerized heart allografts was significantly prolonged. By using irradiated splenocytes from C57BL/6 mice and allogeneic splenocytes from BALB/c mice, a mixed lymphocyte reaction (NILR) assay was performed. The MLR assay used CFSE, and revealed that the splenocytes from the endotoxin-tolerized mice failed to induce the proliferation of allogeneic CD4(+) and CD8(+) T cells. Cytokine analyses of the supernatant of the MLR culture using endotoxin-tolerized stimulators revealed a distinct shift in the Th 1/Th 2 balance toward the Th 2-type response. The induction of ET increased the proportion of myeloid-related dendritic cells (DCs) expressing molecules necessary for antigen presentation, which favor the development of a Th 2 response; however, it reduced the proportion of lymphoid-related DCs expressing those molecules, which favor the development of the Th 1 response. Although the relevance of these findings with regard to the prolonged survival of the endotoxin-tolerized heart allografts remains to be elucidated, this is the first study to demonstrate that the induction of ET in donor animals inhibits alloimmune responses. (C) 2006 Elsevier B.V. All rights reserved.