Epidermal and dermal dendritic cells display differential activation and migratory behavior while sharing the ability to stimulate CD4+ T cell proliferation in vivo
Epidermal and dermal dendritic cells display differential activation and migratory behavior while sharing the ability to stimulate CD4+ T cell proliferation in vivo
复制标题
DOI：
10.4049/jimmunol.181.1.418
复制
发表时间：
2008-07-01
影响因子：
4.4
通讯作者：
Fazekas de St Groth, Barbara
中科院分区：
文献类型：
--
作者：
Shklovskaya, Elena;Roediger, Ben;Fazekas de St Groth, Barbara
最近显示，迁移的朗格汉斯细胞 (m-LC) 仅包含少数皮肤淋巴结中表达朗格汉斯的树突状细胞 (DC)。我们使用 CD45 和 MHC II 类等位基因不同的 BM 嵌合小鼠来明确区分放射抗性 m-LC 和放射敏感性迁移真皮 DC (m-dDC)，以确定它们的表型、对接触致敏的反应以及体内激活初始 CD4(+) T 细胞的能力。我们还表征了 dDC 的三个子集及其迁移对应物，通过 CD11b 和 Langerin 的表达进行区分。皮肤树突状细胞的四个子集中的每一个都表现出响应接触致敏剂而向引流淋巴结的不同迁移。 Langerin(-) CD11b(+) 和 Langerin(+)CD11b(low) dDC 的迁移在 1 天后达到峰值，其次是 Langerin(-)CD11b(low) dDC 在 2 天时和 Langerin(+) LC 在 4 天时。此外，虽然 m-LC 和 m-dDC 在稳态下具有相似的表面表型，但它们对接触致敏表现出意想不到的不同激活反应：m-dDC 在第 1 天显着上调 CD80 和 CD86，而只有 m-LC 上调 CD40，但动力学延迟。因此，m-dDC 可能负责皮肤免疫的初始反应。然而，当同源 MHC II 类的表达仅限于 LC 和 m-LC 时，它们也能够加工和呈递 Ag 蛋白以驱动体内幼稚 CD4 T 细胞增殖。因此，m-dDC 和 m-LC 在皮肤淋巴结中表现出不同的行为，同时具有与 T 细胞特异性相互作用以控制免疫反应的能力。
Migrated Langerhans cells (m-LCs) have recently been shown to comprise only a minority of skin-derived dendritic cells (DCs) expressing Langerin in cutaneous lymph nodes. We have used BM chimeric mice that differ in CD45 and MHC class II alleles to unequivocally distinguish between radioresistant m-LCs and radiosensitive migrated dermal DCs (m-dDCs), to determine their phenotype, response to contact sensitization, and ability to activate naive CD4(+) T cells in vivo. We have also characterized three subsets of dDCs and their migratory counterparts, as distinguished by expression of CD11b and Langerin. Each of the four subsets of skin DCs showed differential migration to draining LN in response to contact sensitizing agents. Migration of Langerin(-) CD11b(+) and Langerin(+)CD11b(low) dDCs peaked after 1 day, followed by Langerin(-)CD11b(low) dDCs at 2 days and Langerin(+) LCs at 4 days. Moreover, while m-LCs and m-dDCs had similar surface phenotypes in the steady state, they displayed unexpectedly different activation responses to contact sensitization: m-dDCs markedly up-regulated CD80 and CD86 at day 1, whereas only m-LCs up-regulated CD40, with delayed kinetics. Thus, m-dDCs are likely to be responsible for the initial response to skin immunization. However, when expression of cognate MHC class II was restricted to LCs and m-LCs, they were also capable of processing and presenting protein Ag to drive naive CD4 T cell proliferation in vivo. Thus, m-dDCs and m-LCs display distinct behavior in cutaneous lymph nodes while sharing the ability to interact specifically with T cells to control the immune response.