很多体外试验结果证明,可溶性葡萄球菌A蛋白(SpA)是人和动物T淋巴细胞和B淋巴细胞的促有丝分裂原和多克隆激活物。T细胞的两个亚群——辅助性T细胞(helper T cell,Th)和抑制性T细胞(Supperssor T coil,Ts)是免疫调节的中心。SpA对活体的...很多体外试验结果证明,可溶性葡萄球菌A蛋白(SpA)是人和动物T淋巴细胞和B淋巴细胞的促有丝分裂原和多克隆激活物。T细胞的两个亚群——辅助性T细胞(helper T cell,Th)和抑制性T细胞(Supperssor T coil,Ts)是免疫调节的中心。SpA对活体的T淋巴细胞及其亚群的影响的研究具有重要的理论和临床意义。现将我们观察的结果报告如下。展开更多
目的用传代人淋巴细胞替代人T淋巴细胞进行猪的免疫,用于试制抗人T细胞猪免疫球蛋白(anti-human T lymphocyte porcine immunoglobulin,P-ATG)免疫猪血浆,并评价其免疫效果。方法大量培养传代人淋巴细胞至免疫所需浓度及数量,采用常规...目的用传代人淋巴细胞替代人T淋巴细胞进行猪的免疫,用于试制抗人T细胞猪免疫球蛋白(anti-human T lymphocyte porcine immunoglobulin,P-ATG)免疫猪血浆,并评价其免疫效果。方法大量培养传代人淋巴细胞至免疫所需浓度及数量,采用常规猪免疫程序进行2次基础免疫及1次加强免疫,获得免疫猪血浆,用E玫瑰花环形成抑制试验和淋巴细胞毒试验进行效价检测。结果3批免疫猪血浆的E玫瑰花环形成抑制试验结果均达到1∶1000(花环形成率均小于对照组平均花环形成率的75%),淋巴细胞毒试验结果均达到1∶500(淋巴细胞死亡率均大于20%),效价均达到《中华人民共和国药典》2015版(三部)中生产用免疫猪血浆的效价标准。结论传代人淋巴细胞可作为人T淋巴细胞的替代免疫原进行猪的免疫,获得了效价合格的免疫猪血浆,用于P-ATG的制备。展开更多
Suberoylanilide hydroxamic acid (SAHA), an orally administered inhibitor of histone deacetylases, is currently in phase II clinical trials for cutaneous T cell lymphomas (CTCL), but the mechanism of SAHA action is unk...Suberoylanilide hydroxamic acid (SAHA), an orally administered inhibitor of histone deacetylases, is currently in phase II clinical trials for cutaneous T cell lymphomas (CTCL), but the mechanism of SAHA action is unknown. In this study, we investigated the anti-tumor effects of SAHA in CTCL cell lines and freshly isolated peripheral blood lymphocytes (PBL) from CTCL patients with high percentage of circulating malignant T cells. Three cell lines (MJ, Hut78, and HH) and PBL from 11 patients and three healthy donors were treated with SAHA (1, 2.5, and 5 μ M) for 24 and/or 48 h. Apoptosis was determined by flow cytometry analysis of sub- G1 hypodiploid nuclei and/or annexin V binding populations. Acetylated histones and apoptosis-associated proteins were detected by Western blotting. SAHA at 1- 5 μ M for 24 and 48 h induced apoptosis in a concentration- and time-dependent manner in three cell lines: MJ (0% - 7% and 1% - 32% ), Hut78 (4% - 36% and 5% - 54% ), and HH (4% - 67% and 8% - 81% ). SAHA at 1- 5 μ M for 48 h also induced more apoptosis of patients’ PBL than healthy donors’ (15% - 32% versus6% - 13% , p<0.05). SAHA treatment caused an accumulation of acetylated histones (H2B, H3, and H4), an increase of p21 WAF1 and bax proteins, a decrease of Stat6 and phospho-Stat6 proteins, and activation of caspase-3 in CTCL cells. Our data suggest that selective induction of malignant T cell apoptosis and modulation of acetylated histones, p21WAF1, bax, Stat6, and caspase-3 may underlie the therapeutic action of SAHA in CTCL patients.展开更多
文摘很多体外试验结果证明,可溶性葡萄球菌A蛋白(SpA)是人和动物T淋巴细胞和B淋巴细胞的促有丝分裂原和多克隆激活物。T细胞的两个亚群——辅助性T细胞(helper T cell,Th)和抑制性T细胞(Supperssor T coil,Ts)是免疫调节的中心。SpA对活体的T淋巴细胞及其亚群的影响的研究具有重要的理论和临床意义。现将我们观察的结果报告如下。
基金supported by the grants from The Special Science and Research Foundation of Wuhan University of Science and Technology(zx0802)the Youth and Middle-Age Scientist Science and Research Foundation of the Affiliated Tianyou Hospital,Wuhan University of Science and Technology(xq2008001)+1 种基金the Foundation of Hubei Provincial Department of Education(530026)the Natural Science Foundation of Jiangxi Province(0640190)
文摘目的用传代人淋巴细胞替代人T淋巴细胞进行猪的免疫,用于试制抗人T细胞猪免疫球蛋白(anti-human T lymphocyte porcine immunoglobulin,P-ATG)免疫猪血浆,并评价其免疫效果。方法大量培养传代人淋巴细胞至免疫所需浓度及数量,采用常规猪免疫程序进行2次基础免疫及1次加强免疫,获得免疫猪血浆,用E玫瑰花环形成抑制试验和淋巴细胞毒试验进行效价检测。结果3批免疫猪血浆的E玫瑰花环形成抑制试验结果均达到1∶1000(花环形成率均小于对照组平均花环形成率的75%),淋巴细胞毒试验结果均达到1∶500(淋巴细胞死亡率均大于20%),效价均达到《中华人民共和国药典》2015版(三部)中生产用免疫猪血浆的效价标准。结论传代人淋巴细胞可作为人T淋巴细胞的替代免疫原进行猪的免疫,获得了效价合格的免疫猪血浆,用于P-ATG的制备。
文摘Suberoylanilide hydroxamic acid (SAHA), an orally administered inhibitor of histone deacetylases, is currently in phase II clinical trials for cutaneous T cell lymphomas (CTCL), but the mechanism of SAHA action is unknown. In this study, we investigated the anti-tumor effects of SAHA in CTCL cell lines and freshly isolated peripheral blood lymphocytes (PBL) from CTCL patients with high percentage of circulating malignant T cells. Three cell lines (MJ, Hut78, and HH) and PBL from 11 patients and three healthy donors were treated with SAHA (1, 2.5, and 5 μ M) for 24 and/or 48 h. Apoptosis was determined by flow cytometry analysis of sub- G1 hypodiploid nuclei and/or annexin V binding populations. Acetylated histones and apoptosis-associated proteins were detected by Western blotting. SAHA at 1- 5 μ M for 24 and 48 h induced apoptosis in a concentration- and time-dependent manner in three cell lines: MJ (0% - 7% and 1% - 32% ), Hut78 (4% - 36% and 5% - 54% ), and HH (4% - 67% and 8% - 81% ). SAHA at 1- 5 μ M for 48 h also induced more apoptosis of patients’ PBL than healthy donors’ (15% - 32% versus6% - 13% , p<0.05). SAHA treatment caused an accumulation of acetylated histones (H2B, H3, and H4), an increase of p21 WAF1 and bax proteins, a decrease of Stat6 and phospho-Stat6 proteins, and activation of caspase-3 in CTCL cells. Our data suggest that selective induction of malignant T cell apoptosis and modulation of acetylated histones, p21WAF1, bax, Stat6, and caspase-3 may underlie the therapeutic action of SAHA in CTCL patients.
