移植前选择性去除同种异体反应供者淋巴细胞预防移植物抗宿主病的实验研究

Experimental study on prevention of graft-versus-host disease by selective elimination of alloreactive donor lymphocytes prior to stem cell transplantation

目的探讨在移植前选择性去除同种异体反应的供者淋巴细胞预防移植物抗宿主病（GVHD）的效果。方法以（BALB／c×C57BL／6）F1雌性小鼠（H-2^d/^b）为受鼠，于第0天接受亚致死量的^60Co γ射线全身照射（TBI），总剂量为4Gy，第1天接种P388D1白血病细胞，第2天输注由C57BL／6雄性小鼠（H-2^b）为供鼠提供的不相匹配的供者脾淋巴细胞，第6天再次TBI 9Gy，第7天输注由（BALB／c×C57BL／6）F1雄性小鼠（H-2^d/^b）提供的骨髓造血干细胞。结果以TBI选择性去除同种异体反应供者淋巴细胞组的小鼠无白血病和GVHD的发生，生存期超过了210d。对照组的小鼠出现了明显的GVHD、白血病或因出血、感染导致的死亡，生存期短，为20～36d（P〈0．01）。结论在造血干细胞移植前输注不相匹配的供者淋巴细胞诱导移植物抗白血病（GVL）效应，然后再选择性去除同种异体反应的供者淋巴细胞来预防GVHD的发生是可行的。

Objective To investigate the effect of prevention of graft-versas-host disease （GVHD） by selective elimination of alloreactive donor lymphocytes prior to stem cell transplantation （SCT）. Methods Female （BALB/c×C57BL/6）F1 mice （H-2^d/^b） as recipients received sublethal total body irradiation （TBI） of 4 Gy （^60Co γ-ray） on day 0 followed by inoculated with P388D1 leukemia cell line on day 1, injection of allogeneic splenocytes supplied by C57BL/6 male mice （H-2^b） on day 2, TBI （9 Gy） were given on day 6. One day later, treated mice were rescued with syngeneic bone marrow cells supplied by （BALB/c×C57BL/6）F1 male mice（H-2^d/^b）. Results Recipients had no occurrence of leukemia and GVHD by selective elimination of alloreactive donor lymphocytes by TBI, survived more than 210 days. Control mice died of evident GVHD, leukemia or the death-related-transplantation within 20 to 36 days （P 〈 0.01）. Conclusion Attempting to induce graft-versus-leukemia （GVL） effects by mismatched lymphocytes given before stem cell transplantation followed by selective elimination of alloreactive donor lymphocytes, thus avoiding lethal GVHD was feasible.