Will A, Blank C, Röllinghoff M, Moll H
Institute of Clinical Microbiology, University of Erlangen, FRG.
Eur J Immunol. 1992 Jun;22(6):1341-7. doi: 10.1002/eji.1830220603.
Cutaneous leishmaniasis is initiated by the bite of an infected sandfly and inoculation of Leishmania major parasites into the mammalian skin. Macrophages are known to play a central role in the course of infection because they are the prime host cells and function as antigen-presenting cells (APC) for induction of the cell-mediated immune response. However, in addition to macrophages in the dermis, the skin contains epidermal Langerhans cells (LC) which can present antigen (Ag) to T cells. Therefore, using a murine model of cutaneous leishmaniasis, we analyzed the ability of epidermal cells to induce a T cell response to L.major. The results demonstrated that freshly isolated LC, but not cultured LC, are highly active in presenting L.major Ag in vitro to T cells from primed mice and to a L.major-specific T cell clone. Furthermore, freshly isolated LC had the ability to retain L.major Ag in immunogenic form for at least 2 days. Their efficiency was much greater than that of irradiated spleen cells, a standard population of APC. LC stimulated both T cell proliferation and production of the lymphokines interleukin (IL)-2 and IL-4. The response was Ag specific and could be induced by lysate of L.major parasites and by live organisms. The data suggest that epidermal LC are important APC in cutaneous leishmaniasis. They may perform a critical function by capturing L.major Ag in the skin and presenting it either to quiescent T cells circulating through the draining lymph node or locally to T effector cells infiltrating the cutaneous lesion.
皮肤利什曼病由受感染的白蛉叮咬引发,利什曼原虫主要寄生虫被接种到哺乳动物皮肤中。已知巨噬细胞在感染过程中起核心作用,因为它们是主要的宿主细胞,并且作为抗原呈递细胞(APC)发挥作用,以诱导细胞介导的免疫反应。然而,除了真皮中的巨噬细胞外,皮肤还含有表皮朗格汉斯细胞(LC),其可以将抗原(Ag)呈递给T细胞。因此,我们使用皮肤利什曼病的小鼠模型,分析了表皮细胞诱导针对利什曼原虫主要种的T细胞反应的能力。结果表明,新鲜分离的LC而非培养的LC,在体外将利什曼原虫主要种Ag呈递给致敏小鼠的T细胞和利什曼原虫主要种特异性T细胞克隆方面具有高度活性。此外,新鲜分离的LC有能力以免疫原性形式保留利什曼原虫主要种Ag至少2天。它们的效率远高于经照射的脾细胞,即APC的标准群体。LC刺激T细胞增殖以及淋巴因子白细胞介素(IL)-2和IL-4的产生。该反应是Ag特异性的,并且可以由利什曼原虫主要种寄生虫的裂解物和活生物体诱导。数据表明表皮LC是皮肤利什曼病中重要的APC。它们可能通过在皮肤中捕获利什曼原虫主要种Ag并将其呈递给通过引流淋巴结循环的静止T细胞或局部呈递给浸润皮肤病变的T效应细胞来发挥关键功能。