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首页> 外文期刊>Transplantation: Official Journal of the Transplantation Society >Antisense deoxyoligonucleotides or antibodies to murine MD-1 inhibit rejection of allogeneic and xenogeneic skin grafts in C3H mice.
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Antisense deoxyoligonucleotides or antibodies to murine MD-1 inhibit rejection of allogeneic and xenogeneic skin grafts in C3H mice.

机译：鼠MD-1的反义脱氧寡核苷酸或抗体可抑制C3H小鼠异体和异种皮肤移植物的排斥。

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BACKGROUND: Altered expression of murine MD-1, a molecule controlling expression of members of the interleukin (IL)-1 receptor family of signaling proteins, regulates antigen-presenting cell-induced alloreactions. We investigated the effect of treatment with antisense deoxyoligonucleotides or antibodies to MD-1 in vivo on allogeneic and xenogeneic skin graft survival and the immune responses in transplanted mice. METHODS: C3H mice received C57BL/6 or Lewis rat skin grafts, followed by i.v. injections of anti-MD-1 antibody or antisense oligonucleotides or control reagents at 48-hr intervals. Survival was monitored. In separate studies, mice were sacrificed at 5-day intervals. Serum was analyzed for circulating MD-1 antigen, and peritoneal cells for surface expression of MD-1. The proliferative and cytolytic response of lymphocytes harvested from treated animals and restimulated in vitro with allo- or xenogeneic cells, and the cytokines produced, was measured. Graft histology was assessed at 11 days after transplantation. RESULTS: Treatment with anti-MD-1 oligonucleotides or antibodies suppressed rejection of both xeno- and allogeneic grafts, decreased induction of graft-specific cytotoxic T cells, increased production of type-2 cytokines (IL-4 and IL-10), and decreased production of type-1 cytokines (IL-2 and interferon-gamma). Serum levels of MD-1 were suppressed, as was expression of MD-1 on the surface of antigen-presenting cells. Grafts from MD-1-treated mice showed little lymphocyte infiltration, and no signs of graft necrosis. CONCLUSION: Our data suggest a critical in vivo role for MD-1 expression in regulating graft rejection, as well as in the concomitant sensitization of T cells and their cytokine production profile, which parallels the rejection response.
机译：背景：鼠MD-1（一种控制信号蛋白白介素（IL）-1受体家族成员表达的分子）的改变表达，调节抗原呈递细胞诱导的同种反应。我们调查了反义的脱氧寡核苷酸或MD-1抗体在体内对同种异体和异种皮肤移植物存活以及移植小鼠免疫反应的影响。方法：C3H小鼠接受C57BL / 6或Lewis大鼠皮肤移植，然后静脉注射。每隔48小时注射一次抗MD-1抗体或反义寡核苷酸或对照试剂。监测生存情况。在单独的研究中，以5天为间隔处死小鼠。分析血清中循环的MD-1抗原，并分析腹膜细胞的MD-1表面表达。测量了从处理过的动物中收集并在体外用同种或异种细胞再刺激的淋巴细胞的增殖和细胞溶解反应，以及产生的细胞因子。移植后第11天评估移植组织学。结果：用抗MD-1寡核苷酸或抗体进行治疗可抑制异种和同种异体移植物的排斥，降低移植物特异性细胞毒性T细胞的诱导，增加2型细胞因子（IL-4和IL-10）的产生，以及降低了1型细胞因子（IL-2和干扰素-γ）的产生。血清MD-1水平被抑制，抗原呈递细胞表面的MD-1表达也被抑制。用MD-1处理过的小鼠的移植物显示出很少的淋巴细胞浸润，并且没有移植坏死的迹象。结论：我们的数据表明，MD-1表达在调节移植排斥以及与T细胞同时发生的敏化及其细胞因子产生过程中具有重要的体内作用，这与排斥反应相平行。

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