Centre d'Immunologie de Marseille-Luminy, UNIV UM2, Aix-Marseille Université, Parc Scientifique et Technologique de Luminy, 13288 Marseille, France; INSERM, Unité Mixte de Recherche 1104, 13288 Marseille, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7280, 13288 Marseille, France;
Institut des Sciences Pharmaceutiques et Biologiques, Université Lyon 1, Université de Lyon, 69373 Lyon, France; Centre National de la Recherche Scientifique, Unite Mixte de Recherche 5286, Département Immunité, Virus et Microenvironnement, Centre de Recherche en Cancérologie de Lyon, 69373 Lyon, France; INSERM U1052, Centre Léon Bérard, 69373 Lyon, France; LabEx DEVweCAN, 69373 Lyon, France;
J Immunol. 2014 Aug 15;193(4):1622-35. doi: 10.4049/jimmunol.1401243. Epub 2014 Jul 9.
Human monocyte-derived dendritic cell (MoDC) have been used in the clinic with moderately encouraging results. Mouse XCR1(+) DC excel at cross-presentation, can be targeted in vivo to induce protective immunity, and share characteristics with XCR1(+) human DC. Assessment of the immunoactivation potential of XCR1(+) human DC is hindered by their paucity in vivo and by their lack of a well-defined in vitro counterpart. We report in this study a protocol generating both XCR1(+) and XCR1(-) human DC in CD34(+) progenitor cultures (CD34-DC). Gene expression profiling, phenotypic characterization, and functional studies demonstrated that XCR1(-) CD34-DC are similar to canonical MoDC, whereas XCR1(+) CD34-DC resemble XCR1(+) blood DC (bDC). XCR1(+) DC were strongly activated by polyinosinic-polycytidylic acid but not LPS, and conversely for MoDC. XCR1(+) DC and MoDC expressed strikingly different patterns of molecules involved in inflammation and in cross-talk with NK or T cells. XCR1(+) CD34-DC but not MoDC efficiently cross-presented a cell-associated Ag upon stimulation by polyinosinic-polycytidylic acid or R848, likewise to what was reported for XCR1(+) bDC. Hence, it is feasible to generate high numbers of bona fide XCR1(+) human DC in vitro as a model to decipher the functions of XCR1(+) bDC and as a potential source of XCR1(+) DC for clinical use.
人源单核细胞衍生的树突状细胞（MoDC）已在临床上得到应用，结果令人鼓舞。鼠源 XCR1(+) DC 在交叉呈递方面表现出色，可在体内靶向诱导保护性免疫，且与 XCR1(+) 人源 DC 具有相似特征。XCR1(+) 人源 DC 的免疫激活潜能评估受到其在体内数量稀少以及缺乏明确的体外对应物的限制。本研究报告了一种在 CD34(+)祖细胞培养物（CD34-DC）中生成 XCR1(+)和 XCR1(-)人源 DC 的方案。基因表达谱分析、表型特征和功能研究表明，XCR1(-) CD34-DC 与人源 MoDC 相似，而 XCR1(+) CD34-DC 类似于 XCR1(+)血源 DC（bDC）。XCR1(+) DC 可被 polyinosinic-polycytidylic acid 强烈激活，但 LPS 不能，而 MoDC 则相反。XCR1(+) DC 和 MoDC 表达的炎症相关分子和与 NK 或 T 细胞相互作用的分子存在显著差异。XCR1(+) CD34-DC 可有效交叉呈递细胞相关抗原，在 polyinosinic-polycytidylic acid 或 R848 刺激下，这与 XCR1(+) bDC 报道的结果一致。因此，体外生成大量真正的 XCR1(+) 人源 DC 作为解析 XCR1(+) bDC 功能的模型，以及作为临床应用的 XCR1(+) DC 的潜在来源是可行的。
