Dendritic cells generated in the presence of granulocyte-macrophage colony-stimulating factor and IFN-α are potent inducers of HIV-specific CD8 T cells
Dendritic cells generated in the presence of granulocyte-macrophage colony-stimulating factor and IFN-α are potent inducers of HIV-specific CD8 T cells
复制标题
DOI：
10.1097/00002030-200308150-00002
复制
发表时间：
2003-08-15
期刊：
影响因子：
3.8
通讯作者：
Weiss, L
中科院分区：
文献类型：
--
作者：
Carbonneil, C;Aouba, A;Weiss, L
目的：研究粒细胞-巨噬细胞集落刺激因子（GM-CSF）和IFN-α诱导外周血单核细胞分化为树突状细胞（DC）的能力及其触发HIV特异性CD 8 T细胞应答的能力。方法：将分离自血清阴性对照和HIV感染者的单核细胞用GM-CSF与IL-4或IFN-α共培养7天分化为DC。我们通过流式细胞术评估表型特征和IL-12产生。通过ELISpot和细胞毒性测定评估DC触发CD 8 T细胞应答的能力。结果：与GM CSF和IL 4诱导的DC相比，GM CSF和IFN α诱导的DC在CD 40连接和金黄色葡萄球菌科万刺激后表达更高水平的MHC I类分子，产生相似或更高水平的IL 12。GM-CSF/IFN-α DC表达低水平的CD 4、CXCR 4和DC-SIGN，并且在分化期间不产生可检测的病毒。发现脉冲的GM-CSF/IFN-α DC引发来自HIV阴性对照的CD 8 T细胞，以对表达HIV抗原的靶细胞发挥细胞毒性活性。HIV肽脉冲的GM-CSF/IFN-α DC促进来自HIV血清阴性供体的自体CD 8 T细胞产生特异性IFN-γ。结论：GM-CSF和IFN-α可诱导产生具有高的CD 8 T细胞刺激能力的DC。因此，这种策略可能代表了一种新的方法，治疗性疫苗接种艾滋病毒疾病。(C)2003年利平科特威廉姆斯威尔金斯。
Objective: To investigate the ability of granulocyte-macrophage colony-stimulating factor (GM-CSF) and IFN-alpha to induce the differentiation of peripheral monocytes into dendritic cells (DC) and their ability to trigger an HIV-specific CD8 T-cell response.Methods: Monocytes isolated from both seronegative controls and HIV-infected individuals were differentiated into DC using GM-CSF with either IL-4 or IFN-alpha for 7 days. We assessed the phenotypic characteristics and IL-12 production by flow cytometry. The ability of DC to trigger CD8 T-cell responses was assessed by means of ELISpot and cytotoxicity assays. In addition, HIV-1-RNA levels were measured in culture supernatants.Results: Compared with control DC generated in the presence of GM-CSF and IL-4, DC generated in the presence of GM-CSF and IFN-alpha expressed higher levels of MHC class I molecules and produced similar or higher levels of IL-12 after CD40 ligation or Staphyloccus aureus Cowan stimulation. GM-CSF/IFN-alpha DC expressed low levels of CD4, CXCR4 and DC-SIGN and did not produce detectable virus during the differentiation period. Pulsed GM-CSF/IFN-alpha DC were found to prime CD8 T cells from HIV-negative controls to exert cytotoxic activity against target cells expressing HIV antigens. HIV peptide-pulsed GM-CSF/IFN-alpha DC promote specific IFN-gamma production by autologous CD8 T cells from HIV-seronegative donors. Furthermore, GM-CSF/IFN-alpha DC from HIV-seropositive patients efficiently present HIV peptides to autologous CD8 T lymphocytes.Conclusion: GM-CSF and IFN-alpha allow the generation of DC with high CD8 T-cell stimulating abilities. Therefore, this strategy may represent a novel approach to therapeutic vaccination in HIV disease. (C) 2003 Lippincott Williams Wilkins.