IMMUNOLOGIC UNRESPONSIVENESS : EXTRATHMIC T CELL DIFFERENTIATION AND PHENOTYPES OF CD8 T CELLS

免疫无反应：CD8 T 细胞的异质性 T 细胞分化和表型

• 批准号: 09671238
• 负责人: YAMAGUCHI Yasuo
• 金额: $ 1.98万
• 依托单位: KUMAMOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671238/
• 关键词: CD8-POSITIVE T CELL; PHENOTYPE; CD45RC; EXTRATHYMIC DIFFERENTIATION; LIVER TRANSPLANTATION; TGF-beta; RAT; IMMUNOLOGIC UNRESPONSIVENESS; liver fransplantation; DST; CD4^+T cell; CD8^+T cell; IL-10; IL-18

A single intravenous injection of freshly heparinized donor-specific blood (DST) prior to transplantation significantly prolonged the survival of fully allogeneic ACI(RT1^a)-to-LEW(RT1^l) rat hepatic allografts. Additionally, pretreatment of LEW rats with PVG.r1 blood, which shares only the RT1. A major histocompatibility complex (MHC) region with ACI, significantly prolonged the survival of ACI hepatic allografts. We report the cellular identity of hepatic allograft leukocyte infiltrates following transplantation.Fluorescence-activated cell sorting (FACS) analysis revealed that CD8^+ T cells infiltrating liver allografts could be divided into two subsets, CD45RC^-CD8^+ and CD45RC^+CD8^+ T cells, and that the ratio of CD4SRC^-CD8^+ T cells/ CD45RC^+CD8^+ T cells was significantly higher in hepatic allografta of recipients pretreated with DST as compared to untreated allografts. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed that CD4SRC^+CD8^+ T cells harvest … More ed from untreated hepatic allografts expressed interleukin (IL)-2 and interferon (IFN)-gamma. In contrast, CD45RC^-CD8^+ T cells from hepatic allografts pretreated with DST expressed IL-4 and IL-1O, but not IL-2. These results indicated that the CD45RC leukocyte common antigen could be used to differentiate CD8^+ T cells following pretreatment with DST.Persistent infiltration of CD4SRC^-CD8^+ T cells, capable of secreting Th2-type cytokines may prevent allograft rejection by causing immunologic unresponsiveness. I addition, the ratio of CD45RC^-CD8^+ T cells/CD45RC^+CD8^+ T cells was significantly higher in hepatic allografts of recipients pretreated with PVO.rl blood compared to untreated allografts.The levels of IEN-gamma, IL-12, and IL-18 mRNA in untreated hepatic allografts were significantly higher than those observed in allografts from recipients pretreated with DST.Transforming growth factor (TGF)-beta and IL-1O mRNA levels in grafts of transfused animals were significantly greater than those in the untreated allograft group. IL-12 and IL-18 mRNA transcripts in an allogeneic mixed lymphocyte reaction were inhibited by IL-10 and TGF-beta. CD4SRC expression was significantly inhibited by TGF-beta, but not IL-1O.Thus CD45RC^-CD8^+T cells expressed IL-4 and IL-1O mRNA and induced by TGF-beta may play an important role in immunologic unresponsiveness induced by donor antigens prior to transplantation. Less

移植前单次静脉注射新鲜肝素化供体特异性血液(DST)可显著延长完全同种异体急性脑梗塞(RT1^a)-LEW(RT1^L)大鼠同种异体肝移植的存活时间。另外，用PVG.r1血液对LEW大鼠进行预处理，这种血液只分享rt1。ACI的主要组织相容性复合体(MHC)区域显著延长了ACI肝移植物的存活时间。我们报道了同种异体肝移植后白细胞的细胞特性。荧光激活细胞分类(FACS)分析表明，CD8^+T细胞可分为CD45RC^-CD8^+和CD45RC^+CD8^+T细胞两个亚群，经DST处理的受者移植肝中CD4SRC^-CD8^+T细胞/CD45RC^+CD8^+T细胞的比例明显高于未经处理的同种异体肝移植。逆转录聚合酶链式反应分析表明，CD4SRC^+CD8^+T细胞可获得…更多未经处理的同种异体肝细胞表达IL-2和干扰素-γ。而经DST处理的同种异体肝移植CD45RC~-CD8~+T细胞表达IL-4和IL-10，但不表达IL-2。提示CD45RC白细胞共同抗原可用于DST预处理后CD8~+T细胞的分化。持续的CD4SRC~+-CD8~+T细胞可分泌Th2型细胞因子，可能通过免疫无应答来预防同种异体移植排斥反应。经PVO血液处理的同种异体肝移植后，CD45RC~+CD8~+T细胞/CD45RC~+CD8~+T细胞的比值显著高于未处理组，未处理组肝组织中IL-18、IL-12和IL-18mRNA水平显著高于DST组，而转化生长因子(TGF)-β和IL-1O mRNA水平显著高于未处理组。IL-10和转化生长因子-β可抑制同种异体混合淋巴细胞反应中IL-12和IL-18mRNA的转录。表达IL-4和IL-10的CD45RC-CD8+T细胞在移植前供者抗原诱导的免疫无应答中可能起重要作用。较少

项目成果

Yamaguchi Y,et al.: "Intracellular calcium affects neutrophil chemoattractant expression by macrophages in rats with cerulein-induced pancreatitis." Digestive Diseases and Sciences. 43. 863-869 (1998)

Yamaguchi Y 等人：“在患有雨蛙蛋白诱导的胰腺炎的大鼠中，细胞内钙影响巨噬细胞中性粒细胞趋化剂的表达。”

Yamaguchi Y,et al.: "Recombinant human hepatocyte growth factor facilitates biliary transport after hepatocyteNtransplantation in Eisai hyperbilirubinemic rats." Dig Dis Sci. 42. 522-528 (1997)

Yamaguchi Y 等人：“重组人肝细胞生长因子促进卫材高胆红素血症大鼠肝细胞移植后的胆汁转运。”

Yamaguchi Y,et al.: "Neutrophil elastase enhances intercellular adhesion molecule-1 expression." Transplantaion. 65. 1622-1628 (1998)

Yamaguchi Y 等人：“中性粒细胞弹性蛋白酶增强细胞间粘附分子 1 的表达。”

Miyanari N,Yamaguchi,et al.: "Pereistent infiliration of CD45RC CD4^+ T cells, Th2-like effector cells in prolonging hepatic allografts in rats pretreated with a donor specific blood transfusion." Hepatology. 25. 1008-1013 (1997)

Miyanari N，Yamaguchi 等人：“在用供体特异性输血预处理的大鼠中，CD45RC CD4^ T 细胞、Th2 样效应细胞在延长同种异体肝移植中的持续浸润。”

Yamaguchi,et al.: "Peroxynitrite formation during rat hepatic allograft refection." Hepatology. in press. (1999)

Yamaguchi 等人：“大鼠肝同种异体移植物感染过程中过氧亚硝酸盐的形成。”