Effect of recombinant human granulocyte colony-stimulating factor on T-lymphocyte function and the mechanism of this effect
Effect of recombinant human granulocyte colony-stimulating factor on T-lymphocyte function and the mechanism of this effect
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DOI：
10.1532/ijh97.a10227
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发表时间：
2004-02-01
影响因子：
2.1
通讯作者：
Huang, XJ
中科院分区：
文献类型：
--
作者：
Chen, SH;Li, X;Huang, XJ
重组人粒细胞集落刺激因子（rhG-CSF）是否直接或间接影响淋巴细胞功能尚有争议。在这项研究中，我们发现，T细胞的增殖反应大大减少，在捐助者接受rhG-CSF的植物血凝素，但部分恢复后，单核细胞被删除。细胞内细胞因子染色显示rhG-CSF处理后供者CD 4（+）细胞中干扰素γ-白细胞介素4的比例下降了5.97倍。未观察到rhG-CSF对离体T细胞功能的影响。rhG-CSF间接诱导淋巴细胞发生显著的定量和定性变化，包括T细胞增殖减少和细胞因子谱的2型辅助T细胞极化。虽然单核细胞抑制T细胞增殖，单核细胞数量的定量变化诱导的抑制活性不能完全解释T淋巴细胞的低反应性。我们认为，必须有另一个调解因素。此外，rhG-CSF治疗后外周血中CD 14（+）CD 86（+）和CD 19（+）CD 80（+）细胞的数量和平均荧光强度均显著下降。B7分子在抗原呈递细胞（单核细胞、B淋巴细胞）上的低表达水平所提供的刺激信号的次优量可能有助于解释T细胞增殖的改变。此外，G-CSF治疗后，外周血中CD 3（+）CD 4（-）CD 8（-）细胞的绝对计数显著增加，并在白细胞分离产物中富集。这些抑制细胞可能导致T细胞低反应性。
Whether recombinant human granulocyte colony-stimulating factor (rhG-CSF) affects lymphocyte function directly or indirectly is controversial. In this study, we found that T-cell proliferation was decreased considerably in response to phytohemagglutinin in donors who received rhG-CSF but was partly restored after monocytes were removed. Intracellular cytokine staining revealed that the interferon gamma-interleukin 4 ratio decreased by 5.97-fold in donor CD4(+) cells after rhG-CSF treatment. No effect of rhG-CSF on ex vivo T-cell function was observed. rhG-CSF indirectly induced significant quantitative and qualitative changes on lymphocytes, including a decrease in T-cell proliferation and type 2 helper T-cell polarization of the cytokine profile. Although monocytes suppressed T-cell proliferation, the suppressive activity induced by the quantitative change in monocyte numbers cannot completely account for the hyporesponsiveness of T-lymphocytes. We believe that there must be another mediating factor. In addition, the numbers and mean fluorescence intensities of CD14(+)CD86(+) cells and CD19(+)CD80(+) cells declined significantly in the peripheral blood after rhG-CSF treatment. Suboptimal amounts of stimulatory signals provided by low expression levels of B7 molecules on antigen-presenting cells (monocytes, B-lymphocytes) may help explain the alteration in T-cell proliferation. In addition, the absolute counts of CD3(+)CD4(-)CD8(-) cells in the peripheral blood were markedly increased and enriched in leukapheresis products following G-CSF treatment. These suppressor cells may contribute to T-cell hyporesponsiveness.