B7配体（CD80和CD86）在CD152介导的同种异体移植耐受中的作用：一项交叉核对假说。

The role of B7 ligands (CD80 and CD86) in CD152-mediated allograft tolerance: a crosscheck hypothesis.

作者信息

Tsai Meng-Kun, Ho Hong-Nerng, Chien Hsiung-Fei, Ou-Yang Pu, Lee Chun-Jean, Lee Po-Huang

机构信息

Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.

出版信息

Transplantation. 2004 Jan 15;77(1):48-54. doi: 10.1097/01.TP.0000107286.21985.EF.

DOI:10.1097/01.TP.0000107286.21985.EF

PMID:14724434

Abstract

BACKGROUND

The regulatory mechanism by which the B7 ligands (CD80 and CD86) direct the CD28/CD152 costimulatory pathways is unclear. This study investigated the role of CD80 and CD86 in a CD152-mediated allograft tolerance model.

METHODS

A low-responding cardiac transplant model (BALB/c-->B10.A) with possible long-term acceptance was used. Immunocytochemical and flow cytometric analyses of the graft-infiltrating cells were conducted to characterize this transplant model. The influence of anti-CD80 and anti-CD86 treatments on the proliferation and interleukin (IL)-2 productions of the tolerated splenocytes (SC) was analyzed. The role of CD80 and CD86 in the induction and maintenance of the graft acceptance in this transplant model were also tested.

RESULTS

B10.A mice could accept the BALA/c cardiac allografts (11/22), and an anti-CD152 antibody blocked the graft acceptance (10/10). Immunocytochemical and flow cytometric analyses showed that CD152+ cells were predominant among the CD4+ cells infiltrating the 100-day grafts of the B10.A recipients (B10.A-100). Either anti-CD80 or anti-CD86 treatment significantly enhanced polyclonal proliferation and IL-2 production of the B10.A-100 SC. Blockade of either CD80 or CD86 prohibited the tolerance transmitted by adoptive transfer, and anti-CD80 or anti-CD86 plus skin grafting undermined the established allograft tolerance.

CONCLUSIONS

Both CD80 and CD86 were essential for the induction and maintenance of the CD152-mediated allograft tolerance.

摘要

背景

B7配体（CD80和CD86）调控CD28/CD152共刺激通路的机制尚不清楚。本研究探讨CD80和CD86在CD152介导的同种异体移植耐受模型中的作用。

方法

采用可能长期存活的低反应性心脏移植模型（BALB/c→B10.A）。对移植浸润细胞进行免疫细胞化学和流式细胞术分析以表征该移植模型。分析抗CD80和抗CD86处理对耐受脾细胞（SC）增殖和白细胞介素（IL）-2产生的影响。还测试了CD80和CD86在该移植模型中诱导和维持移植耐受中的作用。

结果

B10.A小鼠可接受BALB/c心脏异体移植（11/22），而抗CD152抗体可阻断移植耐受（10/10）。免疫细胞化学和流式细胞术分析显示，在浸润B10.A受体100天移植组织的CD4+细胞中，CD152+细胞占主导（B10.A-100）。抗CD80或抗CD86处理均显著增强B10.A-100 SC的多克隆增殖和IL-2产生。阻断CD80或CD86均可阻止过继转移传递的耐受，抗CD80或抗CD86联合皮肤移植会破坏已建立的同种异体移植耐受。