阻断T细胞生长因子信号通路治疗移植物抗宿主病  

Treatment of graft vs host disease by blockage of T cells growth factor receptor pathway

作　　者：陈必成[1] 杨亦荣[2] 昌盛[1] 向芙莉[1] 郭晖[1] 夏鹏[2] 郑少玲[2] 陈忠华 

机构地区：[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

出　　处：《中华器官移植杂志》2006年第12期752-754,共3页Chinese Journal of Organ Transplantation

基　　金：国家自然科学基金资助项目(30271243)

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-2b)脾细胞给F1代小鼠(C57BL／6×Balb／cH-2b/d),建立移植物抗宿主病模型。对GVHD模型小鼠短期内给予抗γ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、天冬氮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。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.

关 键 词：移植物抗宿主病 T淋巴细胞 小鼠 

分 类 号：R617[医药卫生—外科学]