重症肌无力由是乙酰胆碱受体的抗体介导的、具有T细胞依赖性的、同时存在补体参与的神经-肌肉接头处传递障碍的自身免疫性疾病;病变累及神经-肌肉接头处的突触后膜上的乙酰胆碱受体。调节性T细胞(Regulartory T cell,Treg)能够主动抑...重症肌无力由是乙酰胆碱受体的抗体介导的、具有T细胞依赖性的、同时存在补体参与的神经-肌肉接头处传递障碍的自身免疫性疾病;病变累及神经-肌肉接头处的突触后膜上的乙酰胆碱受体。调节性T细胞(Regulartory T cell,Treg)能够主动抑制自身反应性T细胞的活化和增殖,因此可以控制T细胞对自身抗原以及异体抗原的过度反应;它们在重症肌无力的发病过程中起着非常重要的作用。现将Treg细胞的生物学特性、作用机制及在重症肌无力发病中作用作一综述。展开更多
AIM: To assess if a specific cytotoxic T cell response can be induced in patients with malignant liver tumors treated with radio-frequency ablation (RFA). METHODS: Six Patients with liver metastases of colorectal ...AIM: To assess if a specific cytotoxic T cell response can be induced in patients with malignant liver tumors treated with radio-frequency ablation (RFA). METHODS: Six Patients with liver metastases of colorectal cancer and 6 with hepatocellular carcinoma (HCC) underwent RFA. Blood was sampled before, 4 and 8 wk after RFA. Test antigens were autologous liver and tumor lysate obtained from each patient by biopsy. Peripheral T cell activation was assessed by an interferon gamma (IFNγ) secretion assay and flow cytometry. T cells were double-stained for CD4/CD8 and IFNγ to detect cytotoxic T cells. The ratio of IFNγ positive and IFNγ negative T cells was determined as the stimulation index (SI). To assess cytolytic activity, T cells were co-incubated with human CaCo colorectal cancer and HepG2 HCC cells and release of cytosolic adenylate kinase was measured by a luciferase assay. RESULTS: Before RFA SI was 0.021 (±0.006) for CD4^+ and 0.022 (± 0.004) for CD8^+T cells against nonmalignant liver tissue and 0.018 (± 0.005) for CD4^+ and 0.021 (± 0.004) for CD8^+ cells against autologous tumor tissue. Four weeks after RFA SI against tumor tissue increased to 0.109 (± 0.005) for CD4+ and 0.11 (± 0.012) for CD8+ T cells against HCC, and to 0.115 (± 0.031) for CD4^+ and 0.15 (± 0.02) for CD8^+ cells for colorectal metastases (P 〈 0.0001). No increased SI was observed with nonmalignant tumor tissue at all time points. Before RFA cytolytic activity against the respect(ve cancer cells was low with 2.62 (± 0.37) relative luminescence units (RLU), but rose more than 100 fold 4 and 8 wk after RFA. Spontaneous release was 〈 2% of maximum release in all experiments. CONCLUSION: Patients with primary and secondary tumors of the liver show a significant tumor-specific cytotoxic T-cell stimulation with a dramatically increased tumor specific cytolytic activity of CD8^+ T cells after RFA.展开更多
文摘重症肌无力由是乙酰胆碱受体的抗体介导的、具有T细胞依赖性的、同时存在补体参与的神经-肌肉接头处传递障碍的自身免疫性疾病;病变累及神经-肌肉接头处的突触后膜上的乙酰胆碱受体。调节性T细胞(Regulartory T cell,Treg)能够主动抑制自身反应性T细胞的活化和增殖,因此可以控制T细胞对自身抗原以及异体抗原的过度反应;它们在重症肌无力的发病过程中起着非常重要的作用。现将Treg细胞的生物学特性、作用机制及在重症肌无力发病中作用作一综述。
基金Supported by the Bavarian Ministry of Economy (Leitprojekt Medizintechnik) and the Hans L(o|¨)wel Foundation, Bamberg,Germany
文摘AIM: To assess if a specific cytotoxic T cell response can be induced in patients with malignant liver tumors treated with radio-frequency ablation (RFA). METHODS: Six Patients with liver metastases of colorectal cancer and 6 with hepatocellular carcinoma (HCC) underwent RFA. Blood was sampled before, 4 and 8 wk after RFA. Test antigens were autologous liver and tumor lysate obtained from each patient by biopsy. Peripheral T cell activation was assessed by an interferon gamma (IFNγ) secretion assay and flow cytometry. T cells were double-stained for CD4/CD8 and IFNγ to detect cytotoxic T cells. The ratio of IFNγ positive and IFNγ negative T cells was determined as the stimulation index (SI). To assess cytolytic activity, T cells were co-incubated with human CaCo colorectal cancer and HepG2 HCC cells and release of cytosolic adenylate kinase was measured by a luciferase assay. RESULTS: Before RFA SI was 0.021 (±0.006) for CD4^+ and 0.022 (± 0.004) for CD8^+T cells against nonmalignant liver tissue and 0.018 (± 0.005) for CD4^+ and 0.021 (± 0.004) for CD8^+ cells against autologous tumor tissue. Four weeks after RFA SI against tumor tissue increased to 0.109 (± 0.005) for CD4+ and 0.11 (± 0.012) for CD8+ T cells against HCC, and to 0.115 (± 0.031) for CD4^+ and 0.15 (± 0.02) for CD8^+ cells for colorectal metastases (P 〈 0.0001). No increased SI was observed with nonmalignant tumor tissue at all time points. Before RFA cytolytic activity against the respect(ve cancer cells was low with 2.62 (± 0.37) relative luminescence units (RLU), but rose more than 100 fold 4 and 8 wk after RFA. Spontaneous release was 〈 2% of maximum release in all experiments. CONCLUSION: Patients with primary and secondary tumors of the liver show a significant tumor-specific cytotoxic T-cell stimulation with a dramatically increased tumor specific cytolytic activity of CD8^+ T cells after RFA.