Prolonged rat hepatic allograft survival by intrathymic administration of donor antigens : the role of antigen presenting cells (dendritic cells) and Th2 cells

通过胸腺内给予供体抗原延长大鼠同种异体肝移植物的存活：抗原呈递细胞（树突状细胞）和Th2细胞的作用

基本信息

批准号：
06807099
负责人：
YAMAGUCHI Yasuo
金额：
$ 1.28万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06807099/
关键词：
Immunologic tolerance Liver transplantation Rejection Thymus Th2 cells CD4 cells CD8 cells OX22 (CD45RC)

项目摘要

The present sudy was undertaken to investigate the roles of antigen presenting cells (dendritic cells) and Th2 cell for immunologic unresponsiveness induced by preoperative administration of donor antigens in rat hepatic allografts.1).FACS analysis revealed that there were two phenotypes of CD4^+ T cells infiltrated in hepatic allografts, CD45RC^-CD4^+ T and CD45RC^+CD4^+ T cells. RT-PCR demonstrated that CD45RC^-CD4^+ T expressed IL-4 and IL-10 mRNA,suggesting these cells may be Th2-like effector cells.2).The discrimination of Th1 and Th2 cells, which used to be determined by secretory cytokine patterns, could be made by the expression of leukocyte common antigen (CD45RC) on the cell surface.3).CD45RC^-CD4^+ T cells dominantly distributed in prolonging hepatic allografts pretreated with donor antigens. However, these cells were seen in neither spleen nor lymph nodes.4).Plasma levels of hepatocyte growth factor (HGF) in the recipients of hepatic allografts pretreated with donor antigen … More s were significantly higher than those in untreated allograft recipients.5).Immunostaining revealed that HGF^+ cells mainy distributed in the portal areas of hepatic allografts pretreated with donor antigens. HGF^+ cells were also observed in the red pulp of the recipient spleen.6).Double immunostainig demonstrated the phenotypes of HGF^+ cells, HGF^+ED1^+ and HGF^+ED2^+ cells.7).We investigated the implication of increased plasma levels of HGF in prolonging hepatic allografts accumlated mainly by Th2-like effector cells. HGF enhanced the migration of Th2 cells in vitro.8).FACS analysis revealed two phenotypes of CD8^+ T cells infiltrated in hepatic allografts, CD45RC^-CD8^+ and CD45RC^+CD8^+ T cells.9).CD45RC^-CD8^+ T cells significantly increased in hepatic allografts pretreated with donor antigens than untreated allografts. CD45RC^-CD8^+ T cells expressed IL-4 and IL-10 mRNA,suggesting that these cells may be Th2 type cellsIn summary, CD45RC^-CD4^+ T and CD45RC^-CD8^+ T cells significantly increased in prolonging hepatic allografts pretreated with donor antigens. This may be one of the mechanisms underlying immunologic unresponsiveness induced by pretreatment with donor anrigens. Less

本研究旨在探讨抗原呈递细胞（树突状细胞）和Th2细胞在大鼠同种异体肝移植术前给予供体抗原引起的免疫无反应中的作用。1）FACS分析显示CD4^+有两种表型RT-PCR 证实 T 细胞浸润于同种异体肝移植物中，CD45RC^-CD4^+ T 和 CD45RC^+CD4^+ T 细胞。 CD45RC^-CD4^+ T表达IL-4和IL-10 mRNA，表明这些细胞可能是Th2样效应细胞。2).Th1和Th2细胞的区分，过去通过分泌细胞因子模式来确定， 3).CD45RC^-CD4^+ T细胞主要分布在预处理的同种异体肝移植物中然而，这些细胞在脾脏和淋巴结中均未见。4).用供体抗原预处理的同种异体肝移植受者的血浆肝细胞生长因子（HGF）水平显着高于未经处理的同种异体移植物5).免疫染色显示HGF^+细胞主要分布在用HGF^+预处理的同种异体肝移植物的汇管区。在受体脾脏的红髓中也观察到了细胞。6)。双重免疫染色证明了HGF^+细胞、HGF^+ED1^+和HGF^+ED2^+细胞的表型。7)。我们研究了在延长主要由Th2样效应细胞积累的同种异体肝中HGF血浆水平的增加增强了Th2细胞的体外迁移。8).FACS分析揭示了两种表型。同种异体肝移植物中浸润的 CD8^+ T 细胞、CD45RC^-CD8^+ 和 CD45RC^+CD8^+ T 细胞。9)。用供体抗原预处理的同种异体移植肝中的 CD45RC^-CD8^+ T 细胞比未经处理的同种异体移植物显着增加CD45RC^-CD8^+ T 细胞表达 IL-4 和 IL-10 mRNA，表明这些细胞可能是Th2型细胞综上所述，在用供体抗原预处理的同种异体肝移植物中，CD45RC^-CD4^+ T和CD45RC^-CD8^+ T细胞显着增加，这可能是用供体抗原预处理诱导免疫无反应的机制之一。