CD8α- and Langerin-negative dendritic cells, but not Langerhans cells, act as principal antigen-presenting cells in leishmaniasis
CD8α- and Langerin-negative dendritic cells, but not Langerhans cells, act as principal antigen-presenting cells in leishmaniasis
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DOI：
10.1002/eji.200324586
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发表时间：
2004-06-01
影响因子：
5.4
通讯作者：
Körner, H
中科院分区：
文献类型：
--
作者：
Ritter, U;Meissner, A;Körner, H
在利什曼病的早期阶段，三种类型的潜在抗原呈递细胞，包括表皮朗格汉斯细胞 (LC)、真皮树突状细胞 (DC) 和炎症 DC，位于感染部位。因此，哪种细胞类型负责启动保护性免疫反应一直是一个中心问题。在抗利什曼原虫免疫反应的早期阶段，可检测到的利什曼原虫主要抗原位于引流淋巴结（LN）的副皮质中。抗原阳性细胞的表征表明，L. Major 与 CD11c(+) CD8alpha(-) Langerin(-) 表型的 DC 共定位。为了确定抗原摄取面积、真皮或表皮，并进一步确定抗原转运细胞的类型，皮下接种 L. Major，同时用异硫氰酸荧光素 (FITC) 动员 LC。 3天后，携带大利斯特氏菌抗原的DC始终为FITC-，表明源自真皮而不是表皮。此外，将 L. Major 抗原添加到来自 L. Major 感染的 C57BL/6 小鼠引流淋巴结的离体分离的 CD8α(-) 和 CD8α(+) DC 中，证明这两种 DC 亚群都能够在体外刺激抗原特异性 T 细胞增殖。在不添加外源抗原的情况下，只有 CD8a-Langerin DC 能够刺激抗原特异性 T 细胞增殖。因此，我们证明CD8α(-) Langerin(-) DC而不是LC是体内针对细胞内主要利斯特氏菌寄生虫的保护性免疫应答的基础。
In the early phase of leishmaniasis three types of potential antigen-presenting cells, including epidermal Langerhans cells (LC), dermal dendritic cells (DC) and inflammatory DC, are localized at the site of infection. Therefore, it has been a central question which cell type is responsible for the initiation of a protective immune response. In the early stage of an anti-Leishmania immune response, detectable Leishmania major antigen was localized in the paracortex of the draining lymph nodes (LN). Characterization of antigen-positive cells showed that L. major co-localized with DC of a CD11c(+) CD8alpha(-) Langerin(-) phenotype. To determine the area of antigen uptake, dermis or epidermis, and to further define the type of antigen-transporting cells, L. major was inoculated subcutaneously and concurrently LC were mobilized with fluorescein isothiocyanate (FITC). After 3 days, DC carrying L. major antigen were always FITC-, indicating a dermal and not an epidermal origin. Moreover, addition of L. major antigen to ex vivo isolated CD8alpha(-) and CD8alpha(+) DC from the draining LN of L. major-infected C57BL/6 mice demonstrated that both DC subpopulations were able to stimulate antigen-specific T cell proliferation in vitro. Without addition of exogenous antigen only the CD8a- Langerin DC were capable of stimulating antigen-specific T cell proliferation. Thus, we demonstrate that CD8alpha(-) Langerin(-) DC and not LC are the basis of the protective immune response to intracellular L. major parasites in vivo.