Lee Heung Kyu, Zamora Melodie, Linehan Melissa M, Iijima Norifumi, Gonzalez David, Haberman Ann, Iwasaki Akiko
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
J Exp Med. 2009 Feb 16;206(2):359-70. doi: 10.1084/jem.20080601. Epub 2009 Jan 19.
Although mucosal surfaces represent the main portal of entry for pathogens, the mechanism of antigen presentation by dendritic cells (DCs) that patrol various mucosal tissues remains unclear. Instead, much effort has focused on the understanding of initiation of immune responses generated against antigens delivered by injection. We examined the contributions of migratory versus lymph node-resident DC populations in antigen presentation to CD4 and CD8 T cells after needle injection, epicutaneous infection, or vaginal mucosal herpes simplex virus (HSV) 1 infection. We show that upon needle injection, HSV-1 became lymph-borne and was rapidly presented by lymph node-resident DCs to CD4 and CD8 T cells. In contrast, after vaginal HSV-1 infection, antigens were largely presented by tissue-derived migrant DCs with delayed kinetics. In addition, migrant DCs made more frequent contact with HSV-specific T cells after vaginal infection compared with epicutaneous infection. Thus, both migrant and resident DCs play an important role in priming CD8 and CD4 T cell responses, and their relative importance depends on the mode of infection in vivo.
尽管黏膜表面是病原体进入的主要门户，但巡逻于各种黏膜组织的树突状细胞（DC）进行抗原呈递的机制仍不清楚。相反，很多研究致力于理解针对注射递送抗原所产生的免疫反应的起始过程。我们研究了在针刺注射、皮肤感染或阴道黏膜单纯疱疹病毒1（HSV-1）感染后，迁移性DC群体与淋巴结驻留DC群体在向CD4和CD8 T细胞呈递抗原方面的作用。我们发现，针刺注射后，HSV-1通过淋巴传播，并迅速由淋巴结驻留DC呈递给CD4和CD8 T细胞。相比之下，阴道HSV-1感染后，抗原主要由组织来源的迁移性DC呈递，动力学延迟。此外，与皮肤感染相比，阴道感染后迁移性DC与HSV特异性T细胞的接触更频繁。因此，迁移性DC和驻留DC在启动CD8和CD4 T细胞反应中都发挥着重要作用，它们的相对重要性取决于体内的感染方式。
