Tacke Frank, Ginhoux Florent, Jakubzick Claudia, van Rooijen Nico, Merad Miriam, Randolph Gwendalyn J
Department of Gene and Cell Medicine, Icahn Research Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
J Exp Med. 2006 Mar 20;203(3):583-97. doi: 10.1084/jem.20052119. Epub 2006 Feb 21.
Monocytes are circulating precursors for tissue macrophages and dendritic cells (DCs) but are not recognized to directly participate in antigen presentation. We developed techniques to label mouse monocyte subsets with particulate tracers in vivo. Gr-1lo but not Gr-1hi monocytes were stably labeled by intravenous injection of 0.5-microm microspheres. Gr-1hi monocytes could be labeled when the microspheres were injected after systemic depletion of blood monocytes and spleen macrophages. In this condition, the phagocytic tracer was transferred to immature bone marrow monocytes by neutrophils and B cells that first carried the particles to the bone marrow. Moreover, antigens from B cells or proteins conjugated to the tracer particles were processed for presentation by monocytes and could induce T cell responses in the periphery. Cell-associated antigen taken up by bone marrow monocytes was retained intracellularly for presentation of the antigen days later when monocyte-derived DCs migrated to lymph nodes or in vitro after differentiation with granulocyte/macrophage colony-stimulating factor. These data reveal that immature monocytes unexpectedly sample antigen from the bone marrow environment and that they can present these antigens after they leave the bone marrow.
单核细胞是组织巨噬细胞和树突状细胞（DCs）的循环前体，但不被认为直接参与抗原呈递。我们开发了在体内用颗粒示踪剂标记小鼠单核细胞亚群的技术。通过静脉注射0.5微米的微球，可稳定标记Gr-1lo而非Gr-1hi单核细胞。当在全身清除血液单核细胞和脾脏巨噬细胞后注射微球时，Gr-1hi单核细胞也可被标记。在这种情况下，吞噬性示踪剂由首先携带颗粒至骨髓的中性粒细胞和B细胞转移至未成熟的骨髓单核细胞。此外，来自B细胞的抗原或与示踪剂颗粒偶联的蛋白质被单核细胞加工用于呈递，并可在外周诱导T细胞反应。骨髓单核细胞摄取的细胞相关抗原在细胞内保留，数天后当单核细胞衍生的DCs迁移至淋巴结或在体外与粒细胞/巨噬细胞集落刺激因子分化后用于抗原呈递。这些数据表明，未成熟单核细胞意外地从骨髓环境中摄取抗原，并且它们在离开骨髓后能够呈递这些抗原。
