Maldonado-López R, De Smedt T, Michel P, Godfroid J, Pajak B, Heirman C, Thielemans K, Leo O, Urbain J, Moser M
Département de Biologie Moléculaire, Université Libre de Bruxelles, B-1640 Rhode-Saint-Genèse, Belgium.
J Exp Med. 1999 Feb 1;189(3):587-92. doi: 10.1084/jem.189.3.587.
Cells of the dendritic family display some unique properties that confer to them the capacity to sensitize naive T cells in vitro and in vivo. In the mouse, two subclasses of dendritic cells (DCs) have been described that differ by their CD8alpha expression and their localization in lymphoid organs. The physiologic function of both cell populations remains obscure. Studies conducted in vitro have suggested that CD8alpha+ DCs could play a role in the regulation of immune responses, whereas conventional CD8alpha- DCs would be more stimulatory. We report here that both subclasses of DCs efficiently prime antigen-specific T cells in vivo, and direct the development of distinct T helper (Th) populations. Antigen-pulsed CD8alpha+ and CD8alpha- DCs are separated after overnight culture in recombinant granulocyte/macrophage colony-stimulating factor and injected into the footpads of syngeneic mice. Administration of CD8alpha- DCs induces a Th2-type response, whereas injection of CD8alpha+ DCs leads to Th1 differentiation. We further show that interleukin 12 plays a critical role in Th1 development by CD8alpha+ DCs. These findings suggest that the nature of the DC that presents the antigen to naive T cells may dictate the class selection of the adaptative immune response.
树突状细胞家族的细胞具有一些独特的特性，使其能够在体外和体内使幼稚T细胞致敏。在小鼠中，已描述了两类树突状细胞（DC），它们在CD8α表达和在淋巴器官中的定位方面存在差异。这两种细胞群体的生理功能仍不清楚。体外研究表明，CD8α+ DC可能在免疫反应调节中发挥作用，而传统的CD8α- DC则更具刺激性。我们在此报告，这两类DC在体内均能有效地启动抗原特异性T细胞，并指导不同T辅助（Th）群体的发育。在重组粒细胞/巨噬细胞集落刺激因子中过夜培养后，将抗原脉冲的CD8α+和CD8α- DC分离，并注射到同基因小鼠的足垫中。给予CD8α- DC会诱导Th2型反应，而注射CD8α+ DC则导致Th1分化。我们进一步表明，白细胞介素12在CD8α+ DC诱导的Th1发育中起关键作用。这些发现表明，向幼稚T细胞呈递抗原的DC的性质可能决定适应性免疫反应的类别选择。
