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的供体特异性血液（DST）显着延长完全同种异体ACI（RT1^a）至LEW（RT1^1）大鼠同种异体肝移植物的存活时间。此外，用仅共享 RT1 的 PVG.r1 血液对 LEW 大鼠进行预处理。具有 ACI 的主要组织相容性复合体 (MHC) 区域可显着延长 ACI 同种异体肝移植物的存活时间。我们报告了移植后同种异体肝移植物白细胞浸润的细胞身份。荧光激活细胞分选（FACS）分析显示，同种异体肝移植物浸润的 CD8^+ T 细胞可分为两个亚群：CD45RC^-CD8^+ 和 CD45RC^+CD8^+ T 细胞，并且 CD4SRC^-CD8^+ 的比例 与未经处理的同种异体移植物相比，经 DST 预处理的受体同种异体移植肝中的 T 细胞/ CD45RC^+CD8^+ T 细胞显着较高。逆转录酶聚合酶链反应 (RT-PCR) 分析显示，从未经处理的同种异体肝移植物中收获的 CD4SRC^+CD8^+ T 细胞表达白细胞介素 (IL)-2 和干扰素 (IFN)-gamma。相反，来自用DST预处理的同种异体肝移植物的CD45RC^-CD8^+T细胞表达IL-4和IL-10，但不表达IL-2。这些结果表明，在DST预处理后，CD45RC白细胞共同抗原可用于分化CD8^+T细胞。能够分泌Th2型细胞因子的CD4SRC^-CD8^+T细胞的持续浸润可能通过引起免疫无反应来预防同种异体移植排斥。此外，与未处理的同种异体移植物相比，经 PVO.rl 血液预处理的受者同种异体肝移植物中 CD45RC^-CD8^+ T 细胞/CD45RC^+CD8^+ T 细胞的比率显着较高。未经处理的同种异体移植肝中的 IEN-gamma、IL-12 和 IL-18 mRNA 水平显着高于同种异体移植物中观察到的水平 来自经 DST 预处理的受者。输血动物移植物中转化生长因子 (TGF)-β 和 IL-1O mRNA 水平显着高于未处理的同种异体移植物组。同种异体混合淋巴细胞反应中的 IL-12 和 IL-18 mRNA 转录物被 IL-10 和 TGF-β 抑制。 CD4SRC 表达被 TGF-β 显着抑制，但不被 IL-1O 抑制。因此，由 TGF-β 诱导的 CD45RC^-CD8^+T 细胞表达 IL-4 和 IL-1O mRNA，可能在移植前供体抗原诱导的免疫无反应中发挥重要作用。较少的

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。”