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重组人粒细胞集落刺激因子对志愿干细胞供者混合淋巴细胞培养及循环可溶性人类白细胞抗原水平的影响

rhG-CSF effect on mixed lymphocyte cultures and circulating soluble HLA antigen levels in volunteer stem cell donors.

作者信息

Lindemann Monika, Rebmann Vera, Ottinger Hellmut D, Schmolke Keiko, Kreuzfelder Ernst, Grosse-Wilde Hans

机构信息

Institute of Immunology, University Hospital, Essen, Germany.

出版信息

Exp Hematol. 2004 Nov;32(11):1103-9. doi: 10.1016/j.exphem.2004.07.025.

Abstract

OBJECTIVE

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is a cytokine widely used in the procurement of peripheral blood stem cells (PBSC) from donors for allogeneic hematopoietic cell transplantation. Therefore, we were interested in its immediate and long-term effects on cellular and soluble factors known to be involved in the immune response.

METHODS

We studied 35 PBSC donors by mixed lymphocyte culture (MLC) and lymphocyte transformation test (LTT), and 41 for soluble plasma factors (soluble human leukocyte antigen [sHLA]-G, -class I, -DR, and interleukin [IL]-10) pre and 5 days post initial rhG-CSF administration, respectively. In addition, 10 donors were reexamined at an average of 2 months (3-16 weeks) post-rhG-CSF.

RESULTS

At 5 days post-rhG-CSF the donors presented a significant (p < 0.05) decrease of MLC, LTT mitogen, and recall antigen reactions. Plasma levels of sHLA-G, -class I, -DR, and IL-10 (p < 0.005 each) were significantly increased. The changes in IL-10 but not in sHLA were significantly (p < 0.05) correlated with LTT responses. In the 2-month follow-up there was no significant difference in alloreactivity and LTT reactions as compared to the pre-rhG-CSF results. The results generated after 3 to 16 weeks did not depend on the time point of investigation. Consistently, soluble factors decreased to pre-rhG-CSF levels.

CONCLUSIONS

rhG-CSF administration suppresses cellular immune functions within 5 days and increases sHLA and IL-10 plasma levels. These immunomodulatory effects appear to be short-term only and vanished at an average of 2 months after rhG-CSF application.

摘要

目的

重组人粒细胞集落刺激因子(rhG-CSF)是一种细胞因子,广泛用于从供体采集外周血干细胞(PBSC)以进行异基因造血细胞移植。因此,我们对其对已知参与免疫反应的细胞和可溶性因子的即时和长期影响感兴趣。

方法

我们通过混合淋巴细胞培养(MLC)和淋巴细胞转化试验(LTT)研究了35名PBSC供体,并分别在首次给予rhG-CSF前和给药后5天研究了41名供体的可溶性血浆因子(可溶性人类白细胞抗原[sHLA]-G、I类、DR和白细胞介素[IL]-10)。此外,10名供体在rhG-CSF给药后平均2个月(3-16周)接受复查。

结果

rhG-CSF给药后5天,供体的MLC、LTT有丝分裂原和回忆抗原反应显著降低(p<0.05)。sHLA-G、I类、DR和IL-10的血浆水平(各p<0.005)显著升高。IL-10的变化而非sHLA的变化与LTT反应显著相关(p<0.05)。在2个月的随访中,与rhG-CSF给药前的结果相比,同种异体反应性和LTT反应没有显著差异。3至16周后产生的结果不取决于调查时间点。一致地,可溶性因子降至rhG-CSF给药前的水平。

结论

rhG-CSF给药在5天内抑制细胞免疫功能,并增加sHLA和IL-10血浆水平。这些免疫调节作用似乎只是短期的,在rhG-CSF应用后平均2个月消失。

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