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阻断T细胞生长因子信号通路治疗移植物抗宿主病
  • ISSN号:0254-1785
  • 期刊名称:《中华器官移植杂志》
  • 时间:0
  • 分类:R457.7[医药卫生—治疗学;医药卫生—临床医学]
  • 作者机构:[1]华中科技大学同济医学院附属同济医院器官移植研究院教育部/卫生部器官移植国家重点实验室,武汉430030, [2]温州医学院附属第一医院移植中心
  • 相关基金:国家自然科学基金资助项目(30271243)
中文摘要:

目的 探讨通过抗γ公共链单克隆抗体封闭T细胞生长因子受体治疗小鼠移植物抗宿主病(GVHD)的效果。方法 通过混合淋巴细胞培养观察抗γ公共链抗体在体外对T细胞的抑制作用。经静脉输注C57BL/6(H-2^b)脾细胞给F1代小鼠(C57BL/6×Ba1b/cH-2^b/d),建立移植物抗宿主病模型。对GVHD模型小鼠短期内给予抗-/公共链抗体,一共3次,并观察其治疗效果。结果 抗γ公共链抗体可抑制T细胞增殖,使凋亡细胞数增加及M期细胞数下降。输注同种脾细胞能成功建立急性GVHD模型,主要引起肝脏损伤的病理改变。单次注射抗γ公共链抗体可使GVHD小鼠肝内浸润的淋巴细胞发生凋亡;短期内连续3次注射抗γ公共链抗体可使丙氨酸转氨酶、天冬氨酸转氨酶明显低于对照组(P〈0.05),但肝内仍然可观察到淋巴细胞浸润。结论 体外阻断T细胞生长因子受体途径可以完全清除反应性T细胞,亦适用于GVHD治疗;但短期治疗不能完全清除反应性T细胞。

英文摘要:

Objective To investigate the efficacy of anti-common gamma chain (Anti-γc) monoclonal antibodies (mAbs) in the treatment of graft vs host disease (GVHD) by blockage of T cells growth factor receptor pathway. Methods The inhibitory efficacy of Anti-γc mAbs was measured through mixed lymphocytes culture in vitro. 5×10^7 C57BL/6 splenocytes were transfused into F1 (Ba1b/CX C57BL/6, H 2^b/d) via tail vein to develop GVHR model. And injection of anti γc mAbs (0. 5 mg) were given at 1st, 3 rd and 7 th day introperitoneally. Alanine aminotransferase (ALT) and aspartat aminotransferase (AST) levels of plasma were determined to evaluate GVHD. Apoptosis of cells in liver was detected by TUNEL. Results Anti-γc mAhs inhibited T cells proliferation by inducing apoptosis to decrease the number of cells in G2/M phase. Transfusion of splenocytes could successfully develop GVHD model with major injury in liver. Single dose γe mAhs treated was efficacy to induce infiltrating T cells apoptosis in GVHD model. After 3 times of γc mAbs administration, the levels of ALT and AST in treatment group were significantly lower than those in control group (P〈0.05), but infiltrating T cells still could be observed in liver section of both groups. Conclusion Anti-γc mA Conclusion Blockade of γc signaling pathway could fully inhibit T cells proliferation in vitro, but short term administration of Anti-γc mAbs could not completely eliminate allo-reactive T cells in GVHD.

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期刊信息
  • 《中华器官移植杂志》
  • 中国科技核心期刊
  • 主管单位:中国科学技术协会
  • 主办单位:中华医学会
  • 主编:
  • 地址:武汉市江岸区胜利街155号
  • 邮编:430014
  • 邮箱:zhqgyzzz@public.wh.hb.cn
  • 电话:027-82806143
  • 国际标准刊号:ISSN:0254-1785
  • 国内统一刊号:ISSN:42-1203/R
  • 邮发代号:38-27
  • 获奖情况:
  • 国内外数据库收录:
  • 美国化学文摘(网络版),日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2000版)
  • 被引量:8958