Th17细胞和白介素-17在异基因造血干细胞移植aGVHD中的免疫调控分析

Immune regulation of Th17 cells and interleukin-17 in aGVHD after allogeneic hematopoietic stem cell transplantation

目的探讨Th17细胞和白介素-17（IL-17）在异基因造血干细胞移植（allo-HSCT）aGVHD中的免疫调控。方法采用野生型（WT）C57BL/6（H-2b）小鼠与C57BL/6（H-2b）IL-17基因敲除（IL-17-/-）小鼠作为供体,采用BALB/C（H-2b）小鼠作为受体,小鼠给予全身照射8.5 Gy进行清髓性预处理,移植野生型（WT）小鼠1×107个去除T细胞骨髓细胞（TCD-BMCs）以及WT小鼠1×106个CD4＋IL-17-/-T细胞。移植之后每天对小鼠生存状况进行观察1～2次,每隔5 d对aGVHD进行临床评估。收集实验小鼠肝脏、肺、肠以及皮肤,并进行HE染色并进行病理组织学分析,并对移植后Th17细胞组、CD4＋IL-17-/-T细胞组、IL-17-/-BMCs＋IL-17-/-SCs组（KK组）、WT BMCs＋IL-17-/-SCs组（WK组）及WT BMSCs＋WTSCs组（WW组）小鼠的aGVHD积分进行评估。结果 1Th17细胞组移植后5 d、10 d、15 d、20 d aGVHD积分均显著高于IL-17-/-CDD4＋T细胞组（P〈0.05）,且Th17细胞组小鼠平均生存时间显著小于IL-17-/-CDD4＋T细胞组（P〈0.05）；2KK组、WK组及WW组移植后5 d、10 d、15 d、20 d aGVHD积分差异均具有统计学意义（P〈0.05）,且三组平均生存时间方面的差异也均具有统计学意义（P〈0.05）。结论 Th17细胞与IL-17在异基因造血干细胞移植aGVHD中具有较好的免疫调控作用。

Objective To investigate the role of immune regulation of Th17 cells and interleukin-17（ IL-17） in acute graft-versus-host disease（ aGVHD） after allogeneic hematopoietic stem cell transplantation（ allo-HSCT）. Methods Wild-type（ WT） C57 BL / 6（ H-2b） mice and C57 BL / 6（ H-2b） IL-17 knockout（ IL-17-/-） mice were used as donors,BALB / C（ H-2b） mice as recipients. The recipient mice were given myeloablative conditioning with 8. 5 Gy of total body irradiation. 1 × 107T-cell-depleted bone marrow cells（ TCD-BMCs） and 1 × 106CD4 ＋ IL-17-/-T cells of WT mice were transferred. After transplantation daily survival of the mice was observed,clinical assessment of aGVHD was performed at 5 days intervals,and pathological examinations of liver,lung,intestine and skin of mice were analyzed.aGVHD scores were evaluated in Th17 cells and CD4 ＋ IL-17-/-T group,IL-17-/-BMCs ＋ IL-17-/-SCs group（ KK group）,WT BMCs ＋ IL-17-/-SCs group（ WK group） and WT BMSCs ＋ WTSCs group of mice（ WW group）. Results（ 1） 5,10,15 and 20 days after transplantation,aGVHD scores in Th17 cell transplantation group were significantly higher than IL-17-/-CDD4 ＋ T cell group（ P 〈 0.05）,and the average survival time of Th17 cell transplantation group was significantly less than IL-17-/-CDD4 ＋ T cell group（ P 〈 0. 05）.（ 2） There was significant difference in aGVHD scores 5,10,15,and 20 days（ P 〈 0. 05） after transplantation among KK,WK and WW groups; difference in the average survival time among the three groups was also statistically significant（ P 〈 0. 05）. Conclusion Th17 cells and IL-17 play immune regulatory role for the development of aGVHD in allo-HSCT.