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小鼠非清髓外周造血干细胞移植后供者淋巴细胞输注的实验研究 被引量:2

Investigation of donor lymphocytes infusion in mixed hematopoietic murine chimeras after nonmyeloablative peripheral blood stem cell transplantation
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摘要 目的:探讨受者皮肤致敏后的供者淋巴细胞输注对受者嵌合状态的影响及供者嵌合比率与混合淋巴细胞反应(MLR)和受者重建的T细胞亚群间的关系。方法:受鼠C57BL/6小(H-2b)第0天接受X射线全身照射,4小时内移植经rhG-CSF动员后的BALB/c小鼠(H-2d)外周血干细胞2×107个,第2天腹腔注射环磷酰胺200mg/kg,并分别于第28天输注致敏/未致敏的供者淋巴细胞2×106个。结果:移植后第21天模型组小鼠PCR检测结果均呈混合嵌合(MC)状态;致敏后DLI的受鼠60天时转变为完全供者嵌合(CC),CD4+/CD8+T淋巴细胞比值早期下降,60天时有所升高,仍略低于正常水平,MLR呈现供者特异性低反应性;未致敏的DLI受鼠嵌合率虽稍有上升,仍为MC,CD4+/CD8+比值早期升高,后期降至正常水平,MLR供者反应性亦有所下降。结论:经rhG-CSF动员后可以成功建立非清髓性allo-PBSCT小鼠MC模型;经受者皮肤致敏后的DLI能够诱导稳定的CC,高比率嵌合与供者CD4+/CD8+比值下降及MLR的特异性免疫低反应性间具有良好相关性。 Objective:To study the recipient chimerism, the immune state and the dependability between them after infusion of donor lymphocytes(DLI) which were sensitized by the skin of recipient. Methods:Female C57BL/6 mice( H-2^b) as recipients received total body irradiation(TBI) of 5.5 Gy(^60Co X-ray) on day 0 followed by allogeneic peripheral blood stem cell transplantation. The allografts consisted of 2 × 10^7 peripheral hematopoietic stem cells from male BALB/c( H-2^d) donor mice mobilized by granulocyte colonystimulating factor(G-CSF). Two days after allo-HSCT, the recipient mice were given 200 mg/kg cyclophosphamide intraperitoneally. Afterwards these recipient mice were infused with 2 × 10^6 sensitized or tmsensitized-donor lymphocytes at the day of 28 after transplantation. Results:The results showed that the mice which received sensitized-DLI became full-donor chimerism at the 60th day after transplantation. The ratio of CD4^+/CD8^+ T lymphocytes of them decreased during the earher period after DLI and increased half month later, but was still lower than the normal value. Recipients showed the specific hyporesponsiveness to donor mice through MLR assay. In unsensitized group, the mixed-chimeras were maintained, though it increased a little, and the ratio of CD4^+/CD8^+ T lymphocytes increased at first, then decreased to the normal level half month later. The result of MLR also showed hyporesponsiveness, but it exceeded that of the sensitized DLI recipients. Conclusion:Mixed-chimerism could be achieved by using a nonmyeloablative TBI and CTX- based conditioning regimen combination with infusion of peripheral blood stem cells mobilized by rhG-CSF in fully H-2-mismatched recipient mice. Sensitized DLI converted mixed to complete donor chimerism. The rate of CD4^+/CD8^+ and the reactiveness of MLR showed suoer deoendability with the chimerism.
出处 《中国免疫学杂志》 CAS CSCD 北大核心 2006年第9期835-839,共5页 Chinese Journal of Immunology
基金 南京市重大课题 东南大学中大医院重大课题资助项目(编号:YQ0008 2003YJ02)
关键词 非清髓造血干细胞移植 供者淋巴细胞输注 嵌合状态 小鼠 Nonmyeloablative peripheral blood stem cells transplantation Infusion of donor lymphocytes Chimerism Mouse
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参考文献9

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共引文献7

同被引文献21

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