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。
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.