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自体外周血干细胞移植后T淋巴细胞群体中的免疫重建及细胞内细胞因子的产生

Immune reconstitution and production of intracellular cytokines in T lymphocyte populations following autologous peripheral blood stem cell transplantation.

作者信息

Schlenke P, Sheikhzadeh S, Weber K, Wagner T, Kirchner H

机构信息

Institute for Immunology and Transfusion Medicine, University of Lübeck School of Medicine, Germany.

出版信息

Bone Marrow Transplant. 2001 Aug;28(3):251-7. doi: 10.1038/sj.bmt.1703121.

Abstract

For the better understanding of engraftment properties after autologous peripheral blood stem cell transplantation (PBSCT), hematopoietic recovery, immune reconstitution and functional capacity of cytokine production in different lymphocyte populations were examined. In a prospective study, we examined 24 patients suffering from different malignancies after autologous PBSCT. The examination intervals were 1, 3, 6 and 12 months after PBSCT. T cells, B cells and NK cells were analyzed using flow cytometry. The expression and kinetics of cytokines in T lymphocytes were evaluated in 10 patients by intracellular staining of cytokines after PMA/ionomycin stimulation. We observed rapid hematopoietic engraftment proceeding to stable long-term reconstitution. For CD3(+) lymphocytes, a consistent reconstitution associated with an increase in CD3(+)CD8(+) cytotoxic T cells was observed, whereas the CD3(+)CD4(+) helper/inducer T cells remained low (< 200/microl). Impaired B lymphopoiesis with severe depression (<1%) was detected 1 month after PBSCT but recovered thereafter (12.8% after 3 months). The percentages of cytokine-producing T cells and the mean fluorescence intensity (MFI) shifts suggested an insufficient capacity for producing IFNgamma, in particular for CD3(+)CD4(+) T cells, compared to healthy volunteers early after PBSCT. Rapid hematopoietic recovery and partly impaired immune reconstitution, especially regarding the regeneration of B lymphocytes and T helper cells, was observed. The CD4(+) subpopulation remained low throughout the period of examination, whereas the B cells showed a delayed recovery after 3 months. Cytokine production proved to be sufficient after in vitro stimulation in T cell populations with the exception of IFNgamma synthesis.

摘要

为了更好地了解自体外周血干细胞移植(PBSCT)后的植入特性,我们检测了造血恢复、免疫重建以及不同淋巴细胞群体产生细胞因子的功能能力。在一项前瞻性研究中,我们检测了24例自体PBSCT后患有不同恶性肿瘤的患者。检测间隔为PBSCT后的1、3、6和12个月。使用流式细胞术分析T细胞、B细胞和NK细胞。通过PMA/离子霉素刺激后细胞因子的细胞内染色,对10例患者T淋巴细胞中细胞因子的表达和动力学进行了评估。我们观察到造血迅速植入并持续到稳定的长期重建。对于CD3(+)淋巴细胞,观察到其持续重建且CD3(+)CD8(+)细胞毒性T细胞增加,而CD3(+)CD4(+)辅助/诱导T细胞仍然较低(<200/微升)。PBSCT后1个月检测到B淋巴细胞生成受损且严重减少(<1%),但此后恢复(3个月后为12.8%)。与健康志愿者相比,PBSCT后早期,产生细胞因子的T细胞百分比和平均荧光强度(MFI)变化表明产生IFNγ的能力不足,尤其是CD3(+)CD4(+)T细胞。观察到造血迅速恢复且免疫重建部分受损,特别是在B淋巴细胞和T辅助细胞的再生方面。在整个检查期间,CD4(+)亚群一直较低,而B细胞在3个月后显示出延迟恢复。除IFNγ合成外,T细胞群体在体外刺激后细胞因子产生证明是充足的。

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