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

本研究旨在探讨抗原提呈细胞（树突状细胞）和Th2细胞在大鼠同种异体肝移植术前给药供体抗原诱导的免疫无反应中的作用(1)。FACS分析显示，同种异体移植肝组织中浸润的CD4^+ T细胞有两种表型，CD45RC^-CD4^+ T细胞和CD45RC^+CD4^+ T细胞。RT-PCR显示CD45RC^-CD4^+ T表达IL-4和IL-10 mRNA，提示这些细胞可能是th2样效应细胞2)。Th1和Th2细胞的区分，过去是通过分泌细胞因子的模式来确定的，现在可以通过白细胞共同抗原（CD45RC）在细胞表面的表达来确定。CD45RC^-CD4^+ T细胞主要分布于供体抗原预处理过长的同种肝移植物中。然而，这些细胞在脾脏和淋巴结中均未见。经供体抗原预处理的同种异体肝移植受者血浆中肝细胞生长因子（HGF）水平明显高于未处理的同种异体肝移植受者。免疫染色显示HGF^+细胞主要分布于供体抗原预处理的同种异体肝移植物的门静脉区。受体脾红髓中也可见HGF^+细胞(6)。双免疫染色显示HGF^+细胞、HGF^+ED1^+和HGF^+ED2^+细胞的表型(7)。我们研究了血浆HGF水平升高对主要由th2样效应细胞积累的延长肝同种异体移植物的影响。HGF在体外增强Th2细胞的迁移能力8)。FACS分析显示，同种异体肝移植中浸润的CD8^+ T细胞有两种表型，CD45RC^-CD8^+和CD45RC^+CD8^+ T细胞。在供体抗原预处理的同种异体肝移植中，CD45RC^-CD8^+ T细胞明显高于未处理的同种异体肝移植。CD45RC^-CD8^+ T细胞表达IL-4和IL-10 mRNA，提示这些细胞可能是Th2型细胞。综上所述，CD45RC^-CD4^+ T和CD45RC^-CD8^+ T细胞在供体抗原预处理的肝同种异体移植物中显著增加。这可能是供体抗原预处理诱导免疫无反应的机制之一。少

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