供体Treg细胞对小鼠异基因骨髓移植后GVHD和GVL效应的影响

Influence of Donor Treg Cells on GVHD and GVL Effects after Allogeneic Bone Marrow Transplantation in Mice

本研究探讨供体CD4+CD25+调节性T细胞(regulatory T cells,Treg cells)输注对异基因骨髓移植(allo-BMT)后小鼠移植物抗宿主病(GVHD)及移植物抗GVL)效应的影响。建立BALB/c→C57BL/6小鼠EL4白血病骨髓移植模型,体外磁珠分离纯化供鼠CD4+CD25+T细胞,在骨髓移植的同时分别予尾静脉输注CD4+CD25+T细胞、CD4+CD25-T细胞。以移植后生存期、GVHD临床评分、组织病理形态等为观察指标并进行组间比较。结果显示:白血病对照组小鼠平均生存时间为(17.9±0.7)天,均存在白血病细胞浸润;移植对照组及效应T细胞组平均生存时间为(23.2±1.6)天和(22.3±1.9)天,肝脏、皮肤和小肠病理切片显示均存在GVHD病理改变;Treg细胞组小鼠平均生存时间为(47.3±6.5)天,70%的受鼠获得长期存活,病理显示无GVHD及白血病细胞浸润,其GVHD评分较移植对照组及效应T细胞组明显降低(p<0.05)。结论:在小鼠allo-BMT中联合输注供体CD4+CD25+T细胞可减少及减轻GVHD,并保留GVL效应。

In order to explore the influence of purified donor regulatory T cells （Treg） infused after allogeneic bone marrow transplantation （allo-BMT） on GVHD and GVL effect in mice, an EIA leukemia allo-BMT model of BALB/c --C57BL/6 mice was established. The CD4^＋CD25^＋ T cells were purified by positive selection using MACS. The recipients were injected with CD4^＋CD25^＋ T cells orCD4^＋CD25^＋T cells within 4 hours respectively along with allo- BMT. Survival time, clinical GVHD score or histopathological features were observed after allo-BMT. The results showed that the mean survival time in leukemia control group was （ 17.9 ±0.7 ） days and all mice died of leukemia. The mean survival times in transplantation control group and CD4 ＋ CD25 - T group were （ 23.2 ± 1.6 ） and （ 22.3 -±1.9 ） days. Histopathological analysis in several target organs （skin, liver and small intestine） confirmed the presence of severe GVHD. The mean survival time in Treg group was （47.3 ± 6.5 ） days. 70% of recipients were alive until day 60 without features of GVHD or tumor progression. Clinical GVHD scores in Treg group significantly decreased as compared to transplantation control group and CD4^＋CD25^＋ T group （ p 〈 0. 05 ）. It is concluded that aUo-BMT combined with injection of donor CD4^＋CD25^＋ Treg cells can efficiently prevent recipients from lethal GVHD with preserving GVL effect during allo-BMT. Key words