Waithman Jason, Allan Rhys S, Kosaka Hiroshi, Azukizawa Hiroaki, Shortman Ken, Lutz Manfred B, Heath William R, Carbone Francis R, Belz Gabrielle T
Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia.
J Immunol. 2007 Oct 1;179(7):4535-41. doi: 10.4049/jimmunol.179.7.4535.
Skin-draining lymph nodes contain a number of dendritic cell (DC) subsets of different origins. Some of these are migratory, such as the skin-derived epidermal Langerhans cells and a separate dermal DC subset, whereas others are lymphoid resident in nature, such as the CD8+ DCs found throughout the lymphoid tissues. In this study, we examine the DC subset presentation of skin-derived self-Ag by migratory and lymphoid-resident DCs, both in the steady state and under conditions of local skin infection. We show that presentation of self-Ag is confined to skin-derived migrating DCs in both settings. Steady state presentation resulted in deletional T cell tolerance despite these DCs expressing a relatively mature phenotype as measured by traditional markers such as the level of MHC class II and CD86 expression. Thus, self-Ag can be carried to the draining lymph nodes by skin-derived DCs and there presented by these same cells for tolerization of the circulating T cell pool.
引流皮肤的淋巴结包含多个起源不同的树突状细胞（DC）亚群。其中一些是迁移性的，例如源自皮肤的表皮朗格汉斯细胞和一个单独的真皮DC亚群，而其他的本质上是淋巴组织驻留性的，例如在整个淋巴组织中发现的CD8⁺DC。在本研究中，我们研究了迁移性和淋巴组织驻留性DC在稳态和局部皮肤感染条件下对源自皮肤的自身抗原的DC亚群呈递情况。我们发现，在这两种情况下，自身抗原的呈递都局限于源自皮肤的迁移性DC。尽管通过传统标志物（如MHC II类水平和CD86表达水平）测量，这些DC表达相对成熟的表型，但稳态呈递仍导致T细胞删除性耐受。因此，源自皮肤的DC可将自身抗原携带至引流淋巴结，并由这些相同的细胞在那里呈递，以使循环T细胞库产生耐受。
