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

在移植之前，单次静脉注射新鲜肝素化的供体特异性血液（DST）显着延长了完全同种异体ACI（RT1^a）-Lew（RT1^L）大鼠肝合金的存活。此外，用PVG.R1血液对LEW大鼠进行预处理，该血液仅具有RT1。 ACI的主要组织相容性复合物（MHC）区域显着延长了ACI肝合金的存活。我们报告了移植后肝炎同种异体移植白细胞浸润的细胞认同。荧光激活的细胞分选（FACS）分析表明，CD8^+ T细胞浸润肝合金可以分为两种亚群，CD45RC^-CD8^+和CD45RC和CD45RC^+ CD45RC^+ cd45rc^+ t cd45rc^+ cd45rc^+ t和与未经处理的合金CRAFTS相比，在用DST预处理的受体的同种异体移植物中，CD4SRC^-CD8^+ T细胞/ CD45RC^+ CD8^+ T细胞在同种异体的肝炎同种异体移植物中明显更高。逆转录酶聚合酶链反应（RT-PCR）分析表明，CD4SRC^+ CD8^+ T细胞收获…来自未处理的Hepatitic合金表达的介绍了白介素（IL）-2和Interferon（Ifferon）（IFN）-gamma。相比之下，来自DST Express IL-4和IL-1O预处理的肝合金的CD45RC^-CD8^+ T细胞，但不是IL-2。这些结果表明，在用DST进行预处理后，CD45RC白细胞共同抗原可用于区分CD8^+ T细胞。CD4SRC^-CD8^+ T细胞的渗透性可以渗透，能够分泌Th2-type细胞因子，从而可以防止免疫能力降低免疫能力。 i补充，与未经处理的合金相比，用PVO.RL血液预处理的受体中的肝炎合金中，CD45RC^-CD8^+ T细胞/CD45RC^+ CD8^+ T细胞的比率明显更高。从接受DST的受体中的合金生长因素（TGF）-beta和IL-1O mRNA水平在输血动物的移植物中明显大于未经处理的合金组中的动物。 IL-12和TGF-β抑制同种异体混合淋巴细胞反应中的IL-12和IL-18 mRNA转录物。 TGF-beta显着抑制了CD4SRC的表达，但不受IL-1O.CD45RC^-CD8^+T细胞表达IL-4和IL-1O mRNA并由TGF-BETA诱导的TG45RC^-CD8^+T细胞可能在供体抗原抗抗原引起的免疫异能中起重要作用。较少的

项目成果

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 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,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。”

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。”