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

摘要

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)C57BL / 6(H-2b)mice and C57BL / 6(H-2b)IL-17 knockout(IL-17- / -)mice were used as donors,BALB / C(H-2b)mice as recipients. The re-cipient mice were given myeloablative conditioning with 8. 5 Gy of total body irradiation. 1 × 107 T-cell-depleted bone marrow cells( TCD-BMCs)and 1 × 106 CD4+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 af-ter 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.%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。