目的检测免疫性血小板减少症(ITP)患者外周血中CD8^+CD28^-调节性T细胞(Treg)、血小板特异性自身抗体、细胞因子的表达水平,分析其在ITP发病机制以及临床治疗中的意义。方法 73例ITP患者分为激素治疗组( n =42)、重组人粒血小板生成素(r...目的检测免疫性血小板减少症(ITP)患者外周血中CD8^+CD28^-调节性T细胞(Treg)、血小板特异性自身抗体、细胞因子的表达水平,分析其在ITP发病机制以及临床治疗中的意义。方法 73例ITP患者分为激素治疗组( n =42)、重组人粒血小板生成素(rhTPO)治疗组( n =31),并根据治疗效果分为有效组和无效组。流式细胞术检测患者治疗前后外周血CD8^+CD28^- Treg的表达,流式微球技术检测患者外周血血小板特异性自身抗体的表达。ELISA法检测患者治疗前后转化生长因子(TGF)-β1、白介素(IL)-10和干扰素(IFN)-γ表达水平。以30例健康体检者作为正常对照组。结果① 73例ITP患者治疗前CD8^+CD28^-Treg及细胞因子IL-10、TGF-β1的表达低于正常对照组,IFN-γ表达高于正常对照组( P <0.05),激素及rhTPO治疗后有效组CD8^+CD28^- Treg、IL-10、TGF-β1的表达均比治疗前显著上升,IFN-γ的表达较治疗前显著降低( P <0.05)。无效组CD8^+CD28^- Treg、IFN-γ、IL-10、TGF-β1的表达和治疗前相比均未有明显变化。②根据受试者工作特征曲线(ROC),激素组治疗前CD8^+CD28^-Treg的临界值为14.35,此时预测激素疗效的敏感性和特异性分别为66.7%和73.3%。27例有效者中小于14.35的有18例(66.7%),15例无效者中大于14.35的有11例(73.3%)。rhTPO组治疗前CD8^+CD28^-Treg的临界值为15.45,此时预测rhTPO疗效的敏感性和特异性分别为63.6%和88.9%。22例有效者中大于15.45的有14例(63.6%),9例无效者中小于15.45的有8例(88.9%)。③激素组抗血小板膜糖蛋白Ib(GPIb)抗体阳性患者18例,治疗后有效率44.4%,抗GPIb抗体阴性24例,有效率79.1%,两者比较差异有统计学意义( P <0.05)。结论 CD8^+CD28^- Treg及相关细胞因子的表达异常参与了ITP的发病,激素和rhTPO可能通过改变这种异常发挥作用。治疗前检测CD8^+CD28^-Treg有助于预测激素及rhTPO的疗效。抗GPIb抗体阳性可能是激素治疗不敏感的影响因素之一。展开更多
The precise mechanisms responsible for the failure of intrahepatic hepatitis C virus (HCV) specific CD8+T cells to control the virus during persistent infection have not been fully defined. We therefore studied the CD...The precise mechanisms responsible for the failure of intrahepatic hepatitis C virus (HCV) specific CD8+T cells to control the virus during persistent infection have not been fully defined. We therefore studied the CD8+T-cell response in 27 HLA-A2-positive patients using four previously well-defined HLA-A2-restricted HCV epitopes. The corresponding HCV sequences were determined in several patients and compared with the intrahepatic HCV-specific CD8+T-cell response. The results of the study indicate: (1) intrahepatic HCV-specific CD8+T cells are present in the majority of patients with chronic HCV infection and overlap significantly with the response present in the peripheral blood. (2) A large fraction of intrahepatic HCV-specific CD8+T cells are impaired in their ability to secrete interferon γ(IFN-γ). This dysfunction is specific for HCV-specific CD8+T cells, since intrahepatic Flu-specific CD8 +T cells readily secrete this cytokine. (3) T-cell selection of epitope variants may have occurred in some patients. However, it is not an inevitable consequence of a functional virus-specific CD8+T-cell response, since several patients with IFN-γ-producing CD8+T-cell responses harbored HCV sequences identical or cross-reactive with the prototype sequence. (4) The failure of intrahepatic virus-specific CD8 +T cells to sufficiently control the virus occurs despite the presence of virus-specific CD4+T cells at the site of disease. In conclusion, different mechanisms contribute to the failure of intrahepatic CD8+T cells to eliminate HCV infection, despite their persistence and accumulation in the liver.展开更多
Wolfl 等[1]的研究建立了一种以 CD137为表面标记，从人 CD8＋T 细胞中快速鉴定和分离抗原特异性 T 细胞的方法。由于 CD137分子表达于活化的 CD4^＋和 CD8^＋T 细胞表面[2]，其表达上调依赖于 T 细胞经抗原刺激后活化，并可在抗原刺激...Wolfl 等[1]的研究建立了一种以 CD137为表面标记，从人 CD8＋T 细胞中快速鉴定和分离抗原特异性 T 细胞的方法。由于 CD137分子表达于活化的 CD4^＋和 CD8^＋T 细胞表面[2]，其表达上调依赖于 T 细胞经抗原刺激后活化，并可在抗原刺激后12 h ~5 d 内持续表达[3]。因此可以CD137为标记，从 T 细胞中检测和分离比例较低的抗原特异性 T 细胞。展开更多
文摘目的检测免疫性血小板减少症(ITP)患者外周血中CD8^+CD28^-调节性T细胞(Treg)、血小板特异性自身抗体、细胞因子的表达水平,分析其在ITP发病机制以及临床治疗中的意义。方法 73例ITP患者分为激素治疗组( n =42)、重组人粒血小板生成素(rhTPO)治疗组( n =31),并根据治疗效果分为有效组和无效组。流式细胞术检测患者治疗前后外周血CD8^+CD28^- Treg的表达,流式微球技术检测患者外周血血小板特异性自身抗体的表达。ELISA法检测患者治疗前后转化生长因子(TGF)-β1、白介素(IL)-10和干扰素(IFN)-γ表达水平。以30例健康体检者作为正常对照组。结果① 73例ITP患者治疗前CD8^+CD28^-Treg及细胞因子IL-10、TGF-β1的表达低于正常对照组,IFN-γ表达高于正常对照组( P <0.05),激素及rhTPO治疗后有效组CD8^+CD28^- Treg、IL-10、TGF-β1的表达均比治疗前显著上升,IFN-γ的表达较治疗前显著降低( P <0.05)。无效组CD8^+CD28^- Treg、IFN-γ、IL-10、TGF-β1的表达和治疗前相比均未有明显变化。②根据受试者工作特征曲线(ROC),激素组治疗前CD8^+CD28^-Treg的临界值为14.35,此时预测激素疗效的敏感性和特异性分别为66.7%和73.3%。27例有效者中小于14.35的有18例(66.7%),15例无效者中大于14.35的有11例(73.3%)。rhTPO组治疗前CD8^+CD28^-Treg的临界值为15.45,此时预测rhTPO疗效的敏感性和特异性分别为63.6%和88.9%。22例有效者中大于15.45的有14例(63.6%),9例无效者中小于15.45的有8例(88.9%)。③激素组抗血小板膜糖蛋白Ib(GPIb)抗体阳性患者18例,治疗后有效率44.4%,抗GPIb抗体阴性24例,有效率79.1%,两者比较差异有统计学意义( P <0.05)。结论 CD8^+CD28^- Treg及相关细胞因子的表达异常参与了ITP的发病,激素和rhTPO可能通过改变这种异常发挥作用。治疗前检测CD8^+CD28^-Treg有助于预测激素及rhTPO的疗效。抗GPIb抗体阳性可能是激素治疗不敏感的影响因素之一。
文摘The precise mechanisms responsible for the failure of intrahepatic hepatitis C virus (HCV) specific CD8+T cells to control the virus during persistent infection have not been fully defined. We therefore studied the CD8+T-cell response in 27 HLA-A2-positive patients using four previously well-defined HLA-A2-restricted HCV epitopes. The corresponding HCV sequences were determined in several patients and compared with the intrahepatic HCV-specific CD8+T-cell response. The results of the study indicate: (1) intrahepatic HCV-specific CD8+T cells are present in the majority of patients with chronic HCV infection and overlap significantly with the response present in the peripheral blood. (2) A large fraction of intrahepatic HCV-specific CD8+T cells are impaired in their ability to secrete interferon γ(IFN-γ). This dysfunction is specific for HCV-specific CD8+T cells, since intrahepatic Flu-specific CD8 +T cells readily secrete this cytokine. (3) T-cell selection of epitope variants may have occurred in some patients. However, it is not an inevitable consequence of a functional virus-specific CD8+T-cell response, since several patients with IFN-γ-producing CD8+T-cell responses harbored HCV sequences identical or cross-reactive with the prototype sequence. (4) The failure of intrahepatic virus-specific CD8 +T cells to sufficiently control the virus occurs despite the presence of virus-specific CD4+T cells at the site of disease. In conclusion, different mechanisms contribute to the failure of intrahepatic CD8+T cells to eliminate HCV infection, despite their persistence and accumulation in the liver.
文摘Wolfl 等[1]的研究建立了一种以 CD137为表面标记，从人 CD8＋T 细胞中快速鉴定和分离抗原特异性 T 细胞的方法。由于 CD137分子表达于活化的 CD4^＋和 CD8^＋T 细胞表面[2]，其表达上调依赖于 T 细胞经抗原刺激后活化，并可在抗原刺激后12 h ~5 d 内持续表达[3]。因此可以CD137为标记，从 T 细胞中检测和分离比例较低的抗原特异性 T 细胞。
