Sorbonne Universités, UPMC Université Paris 06, INSERM, Centre d'Immunologie et des Maladies Infectieuses, Paris, France.
Laboratoire de Biologie Tissulaire et d'Ingénierie Thérapeutique, Unité Mixte de Recherche 5305, Université Lyon 1, Centre National de la Recherche Scientifique (CNRS), Institut de Biologie et Chimie des Protéines (IBCP)-Lyon, France.
J Invest Dermatol. 2017 Sep;137(9):1905-1913. doi: 10.1016/j.jid.2017.04.016. Epub 2017 Apr 28.
Intradermal delivery of antigen represents a potent route of immunization that involves multiple blood- and skin-derived dendritic cell subpopulations endowed with specialized functions and dynamics in their ability to prime naïve CD4 T cells in the draining lymph nodes. However, their individual contributions to the generation of CD4 T follicular helper (T) cells and germinal centers (GCs) remain to be understood. We found that intradermal immunization of mice with a particle-based vaccine induced robust T and germinal center B-cell responses in skin draining lymph nodes, which were completely abrogated when skin cell emigration was prevented. However, in this later condition, both lymph node-resident and blood-derived inflammatory cells access the antigen in the draining lymph nodes but are not able to induce T cell differentiation. Rather, only skin-derived dendritic cells up-regulated key genes related to T cell development in the draining lymph nodes. Depletion of Langerhans cells partially abrogated T and germinal center B-cell responses. Thus, after intradermal immunization, only skin-derived migratory dendritic cells, including Langerhans cells, permit the generation of T cells and germinal centers. Identifying the relative contributions of tissue and lymphoid organ dendritic cell subsets in generating humoral immune responses is of great importance for the development of tailored vaccines.
皮内递送抗原代表了一种有效的免疫途径，涉及多种血液和皮肤来源的树突状细胞亚群，这些细胞具有特殊的功能和动力学特性，能够在引流淋巴结中激活初始 CD4 T 细胞。然而，它们在产生 CD4 T 滤泡辅助（Tfh）细胞和生发中心（GC）方面的个体贡献仍有待了解。我们发现，用基于颗粒的疫苗对小鼠进行皮内免疫会在引流淋巴结中引起强烈的 T 和生发中心 B 细胞反应，而当阻止皮肤细胞迁移时，这种反应会完全被阻断。然而，在后一种情况下，淋巴结驻留细胞和血液来源的炎症细胞都可以进入引流淋巴结中的抗原，但不能诱导 T 细胞分化。相反，只有皮肤来源的树突状细胞在引流淋巴结中上调与 T 细胞发育相关的关键基因。耗尽朗格汉斯细胞会部分阻断 T 和生发中心 B 细胞的反应。因此，在皮内免疫后，只有皮肤来源的迁移树突状细胞（包括朗格汉斯细胞）才能产生 T 细胞和生发中心。确定组织和淋巴器官树突状细胞亚群在产生体液免疫反应中的相对贡献，对于定制疫苗的开发非常重要。
