DENDRITIC CELLS IN LEISHMANIA MAJOR-IMMUNE MICE HARBOR PERSISTENT PARASITES AND MEDIATE AN ANTIGEN-SPECIFIC T-CELL IMMUNE-RESPONSE
DENDRITIC CELLS IN LEISHMANIA MAJOR-IMMUNE MICE HARBOR PERSISTENT PARASITES AND MEDIATE AN ANTIGEN-SPECIFIC T-CELL IMMUNE-RESPONSE
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DOI：
10.1002/eji.1830250310
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发表时间：
1995-03-01
影响因子：
5.4
通讯作者：
ROLLINGHOFF, M
中科院分区：
文献类型：
--
作者：
MOLL, H;FLOHE, S;ROLLINGHOFF, M
在感染了人皮肤利什曼病的一种病因--硕大利什曼原虫后，耐药品系的小鼠能够控制感染，病变自发消退。持久的细胞介导的免疫保护他们免受再感染。尽管如此，这些小鼠的淋巴结中仍存在少量存活的寄生虫。我们最近发现，除了巨噬细胞外，表皮朗格汉斯细胞也能摄取L。少校此外，朗格汉斯细胞具有将活寄生虫从感染的皮肤运输到引流淋巴结以呈递给抗原特异性T细胞并引发细胞免疫应答的独特能力。在迁移过程中，朗格汉斯细胞发育成树突状细胞。在本研究中，我们分析了树突状细胞是否支持寄生虫在免疫宿主中的持续存在。免疫组织学研究和体外试验表明，在感染L。主要是，巨噬细胞和树突状细胞都含有活的寄生虫。然而，只有树突状细胞能够诱导对L。主要在体外无外源性抗原的情况下。在体内进行的跟踪实验表明，淋巴结中受感染的树突状细胞来自皮肤迁移的朗格汉斯细胞。数据表明L.免疫动物淋巴结中主要感染的树突细胞和巨噬细胞代表长期宿主细胞，但只有树突细胞具有将内源性寄生虫抗原呈递给T细胞的能力。因此，长期感染的树突状细胞可以持续刺激寄生虫特异性T细胞群，保护小鼠免受再感染。我们的研究结果支持这一假设，即抗原的持久性支持T细胞记忆的维持，树突状细胞在这一过程中至关重要。
Upon infection with Leishmania major, a cause of human cutaneous leishmaniasis, mice of resistant strains are able to control the infection,with lesions resolving spontaneously. A long-lasting cell-mediated immunity protects them from reinfection. Nevertheless, small numbers of viable parasites persist in the lymph nodes of these mice. We have recently documented that, in addition to macrophages, epidermal Langerhans cells can ingest L. major. Furthermore, Langerhans cells have the unique ability to transport viable parasites from the infected skin to the draining lymph node for presentation to antigen-specific T cells and initiation of the cellular immune response. During migration, Langerhans cells develop into dendritic cells. In the present study, we analyzed whether dendritic cells support the persistence of parasites in immune hosts. Immunohistological studies and assays in vitro showed that in the lymph nodes of mice that have recovered from infection with L. major, both macrophages and dendritic cells harbor viable parasites. However, only dendritic cells were able to induce a vigorous T-cell immune response to L. major in vitro in the absence of exogenous antigen. Tracking experiments conducted in vivo suggested that the infected dendritic cells in the lymph nodes are derived from Langerhans cells that have emigrated from the skin. The data demonstrate that L. major-infected dendritic cells and macrophages in lymph nodes of immune animals represent long-term host cells, but only dendritic cells have the ability to present endogenous parasite antigen to T cells. Long-term infected dendritic cells may thus allow the sustained stimulation of a population of parasite-specific T cells, protecting the mice from reinfection. Our results favor the hypothesis that the persistence of antigen supports the maintenance of T cell memory and that dendritic cells are critically involved in this process.