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

• 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)

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提呈细胞（树突状细胞）和Th 2细胞在术前给予供体抗原诱导大鼠肝移植免疫无反应中的作用。1）流式细胞仪分析表明，移植肝中浸润的CD 4 ^+ T细胞有两种表型：CD 45 RC ^-CD 4 ^+ T细胞和CD 45 RC ^+ CD 4 ^+ T细胞。RT-PCR结果显示，CD 45 RC ^-CD 4 ^+ T细胞表达IL-4和IL-10 mRNA，提示这些细胞可能是Th 2类效应细胞。3）CD45RC ^-CD4^+供者抗原预处理的肝移植物中T细胞占优势。4）供者抗原预处理后肝移植受者血浆肝细胞生长因子（HGF）水平的变化 ...更多信息 免疫组化染色显示，经供体抗原预处理后的移植肝，HGF^+细胞主要分布于汇管区。6）免疫组化双重染色显示肝细胞生长因子^+细胞、肝细胞生长因子^+内皮素1 ^+细胞和肝细胞生长因子^+内皮素2 ^+细胞的表型。7）我们研究了血浆中肝细胞生长因子水平升高在延长主要由Th 2样效应细胞介导的肝移植物存活时间中的意义。体外实验表明，HGF可促进Th 2细胞的迁移。8）流式细胞仪分析显示，移植肝中浸润的CD 8 ^+ T细胞有两种表型，即CD 45 RC ^-CD 8 ^+和CD 45 RC ^+ CD 8 ^+ T细胞。9）与未处理的移植肝相比，经供体抗原预处理的移植肝中CD 45 RC ^-CD 8 ^+ T细胞显著增加。结果表明，在供者抗原预处理的肝移植物中，CD 45 RC ^-CD 8 ^+ T细胞和CD 45 RC ^-CD 4 ^+ T细胞均表达IL-4和IL-10 mRNA，提示这些细胞可能是Th 2型细胞。这可能是供体抗原预处理诱导免疫无反应的机制之一。少

项目成果

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Miyanari N：“大鼠肝移植后胸腺中的 T 细胞反应。”

Yamaguchi Y,et al.: "Proliferative activity in the splenic compartment during hepatic allograft rejection in the rat." Transplant Proc. 27. 1614-1616 (1995)

Yamaguchi Y 等人：“大鼠肝同种异体移植排斥期间脾室的增殖活性。”

Ichiguchi O: "Plasma levels of hepatocyte growth factor in prolonging hepatic allografts in rats pretreated with donor-specific blood transfusion." Transplant Proc. 27. 1634-1636 (1995)

Ichiguchi O：“经供者特异性输血预处理的大鼠中肝细胞生长因子的血浆水平可延长同种异体肝移植。”

Hisama N: "Ischemia-reperfusion injury : the role of Kupffer cells in the production of cytokine-induced neutrophil chemoattractant (CINC) ,a member of the interleukin-8 family." Transplant Proc. 27. 1604-1606 (1995)

Hisama N：“缺血再灌注损伤：库普弗细胞在细胞因子诱导的中性粒细胞趋化剂 (CINC)（白细胞介素 8 家族成员之一）的产生中的作用。”

Goto M: "Suppression of hepatic allograft rejection in the rat by Mitomycin C-treated donor splenocytes : Tissue distribution of donor class I major histocompatibility complex antigen-positive cells in the recipient." Transplant Proc. 27. 1625-1627 (1995)

Goto M：“丝裂霉素 C 处理的供体脾细胞对大鼠肝同种异体移植排斥的抑制：供体 I 类主要组织相容性复合物抗原阳性细胞在受体中的组织分布。”