淋巴细胞缺乏状态对白血病特异性细胞毒性T淋巴细胞体内抗白血病效应的影响

Recipient lymphopenia state enhances the expansion and anti-leukemia effect of leukemia specific cytotoxic T lymphocytes

目的探讨淋巴细胞缺乏状态对白血病特异性细胞毒性T淋巴细胞(CTL)体内增殖和抗白血病作用的影响。方法采用6 Gy照射C57BL/6小鼠诱导淋巴细胞缺乏状态,分别经尾静脉注射EGFP+C57BL/6小鼠脾T淋巴细胞和白血病特异性CTL,随后皮下接种1×106FBL3白血病细胞。用流式细胞仪分析小鼠外周血EGFP+细胞及T淋巴细胞亚群比例,同时观察脾T淋巴细胞和白血病特异性CTL对随后接种的FBL3白血病细胞的杀伤作用。结果在淋巴细胞缺乏状态下输入的脾T淋巴细胞和白血病特异性CTL均可得到有效扩增(第18天输注脾T淋巴细胞组和输注CTL组外周血中EGFP+细胞比例分别为28.81%和42.24%),但脾T淋巴细胞对随后接种的白血病细胞生长无抑制作用,而白血病特异性CTL在淋巴细胞缺乏受体小鼠体内扩增速度更快,扩增的倍数更高,并具有显著增强的抗白血病作用。结论诱导受体淋巴细胞缺乏可显著增强外源性CTL输注的疗效。

Objective To determine the role of recipient lymphopenia state in the expansion and function of leukemia specific cytotoxic T lymphocytes (CTLs).Methods C57BL/6 mice were induced to lymphopenia with 6Gy total body irradiation. Spleen T cells or leukemia specific T cells from EGFP^+ transgenic C57BL/6-EGFP mice were adoptively transferred by intravenous injection. The mice were challenged subcutaneously with 1×10^(6) FBL3 leukemic cells at day 2 after irradiation. The peripheral WBC count, percentage of EGFP^+ cells, subsets of T cells and tumor sizes were monitored.Result Both of the spleen T cell and leukemia specific CTL proliferated efficiently with the pencentage of EGFP^+ cells of 28.81% and (42.24%), respectively, after infused into lymphopenic recipients. However, spleen T cells had no anti-leukemia effect regardless of its expansion. In contrast, leukemia specific CTLs showed a more rapid and extensive expansion under the condition of lymphopenia and a enhanced anti-leukemia immunity.Conclusion Transfusion of leukemia specific CTLs under lymphopenia state could be a feasible strategy to expand leukemia specific CTLs and generate favorable anti-leukemia effect in vivo.