Monocyte-derived dendritic cells generated after a short-term culture with IFN-α and granulocyte-macrophage colony-stimulating factor stimulate a potent Epstein-Barr virus-specific CD8+ T cell response
Monocyte-derived dendritic cells generated after a short-term culture with IFN-α and granulocyte-macrophage colony-stimulating factor stimulate a potent Epstein-Barr virus-specific CD8+ T cell response
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DOI：
10.4049/jimmunol.170.10.5195
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发表时间：
2003-05-15
影响因子：
4.4
通讯作者：
Ferrantini, M
中科院分区：
文献类型：
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作者：
Santodonato, L;D'Agostino, G;Ferrantini, M
细胞免疫应答对于控制EBV相关淋巴增生性疾病至关重要。为了诱导抗EBV细胞介导的免疫，我们使用了在GM-CSF和I型IFN（IFN-DCs）存在下通过人CD 14（+）单核细胞的3天培养产生的树突状细胞（DCs），并用对应于CTL EBV表位的肽脉冲。将IFN-DC的功能活性与通过用GM-CSF和IL-4培养单核细胞3天分化的APC的功能活性进行比较，并表示为IL-4-DC。用EBV肽脉冲的自体IFN-DC刺激来自EBV血清阳性供体的PBL导致产生IFN-γ的特异性T淋巴细胞相对于用负载肽的IL-4-130刺激更强的扩增，如通过ELISPOT测定所评估的。当纯化的CD 8（+）T细胞与EBV肽致敏的IFN-DCs或IL-4-DCs共培养时，在IFN-DCs刺激的CD 8（+）T细胞培养物中观察到显著更高水平的特异性细胞毒活性。将肽脉冲的IFN-DCs注射到移植有自体PBL的SCED小鼠中，导致从脾和腹腔中回收的EBV特异性人CD 8（+）T细胞的数量显著高于注射肽脉冲的IL-4-DCs的小鼠。此外，当将肽脉冲的IFN-DCs注射到用具有高淋巴瘤诱导能力的PBMC重建的SCED小鼠中时，观察到淋巴瘤发展的显著延迟，而注射未脉冲的IFN-DCs无效。我们的研究结果表明，IFN-DCs在体外和体内有效地促进CD 8（+）T淋巴细胞作为细胞毒性效应器对EBV转化细胞的扩增。
Cellular immune responses are crucial for the control of EBV-associated lymphoproliferative diseases. To induce an anti-EBV cell-mediated immunity, we have used dendritic cells (DCs) generated by a 3-day culture of human CD14(+) monocytes in the presence of GM-CSF and type I IFN (IFN-DCs) and pulsed with peptides corresponding to CTL EBV epitopes. The functional activity of IFN-DCs was compared with that of APCs differentiated by culturing monocytes for 3 days with GM-CSF and IL-4 and indicated as IL-4-DCs. Stimulation of PBLs from EBV-seropositive donors with EBV peptide-pulsed autologous IFN-DCs resulted in a stronger expansion of specific T lymphocytes producing IFN-gamma with respect to stimulation with peptide-loaded IL-4-130, as assessed by ELISPOT assays. When purified CD8(+) T cells were cocultured with EBV peptide-pulsed IFN-DCs or IL-4-DCs, significantly higher levels of specific cytotoxic activity were observed in CD8(+) T cell cultures stimulated with IFN-DCs. Injection of peptide-pulsed IFN-DCs into SCED mice transplanted with autologous PBLs led to the recovery of a significantly greater number of EBV-specific human CD8(+) T cells from the spleen and the peritoneal cavity with respect to that recovered from mice injected with peptide-pulsed IL-4-DCs. Moreover, a significant delay in lymphoma development was observed when peptide-pulsed IFN-DCs were injected into SCED mice reconstituted with PBMCs endowed with a high capability of lymphoma induction, whereas injection of unpulsed IFN-DCs was ineffective. Our results indicate that IFN-DCs efficiently promote in vitro and in vivo the expansion of CD8(+) T lymphocytes acting as cytotoxic effectors against EBV-transformed cells.