Duraiswamy N, Tse Y, Hammerberg C, Kang S, Cooper K D
Department of Dermatology, University of Michigan, Ann Arbor 48109-0530.
J Invest Dermatol. 1994 Nov;103(5):678-83. doi: 10.1111/1523-1747.ep12398513.
Dermal cells are capable of initiating contact-hypersensitivity responses but the precise identification of the antigen-presenting cell within murine dermis is lacking. Class II major histocompatibility complex (MHC)+ cells with dendritic shape and lacking endothelial factor VIII but expressing the dendritic antigen-presenting cell marker NLDC-145 were observed in the perivascular and interstitial dermis of BALB/c and C3H/HeN skin. The heterogeneous class II MHC+ cells could be divided into two subsets: each was class II MHC+ CD45+ (bone marrow derived) GR-1- (non-neutrophil/macrophage) CD3- (non T), but one subset was CD11b+ (beta 2 integrin) and the other was CD11b-. Ultrastructural examination of class II MHC+ cells revealed the presence of a Langerhans cell-like/indeterminant cell subset with indented nuclei, dendritic morphology, active cytoplasm, and dense intermediate filaments. Phagolysomes and Birbeck granules were not observed in such cells, indicating these were distinct from dermal macrophages and from classical epidermal Langerhans cells, respectively. Cells with a monocyte/macrophage ultrastructural appearance were also noted, likely representing the class II MHC subset expressing CD11b and Ly6c (monocyte/endothelial antigen). Dermal cells in suspension were capable of processing and presenting large protein antigens to antigen-specific T-cell hybridomas; dermal cells also induced the syngeneic mixed lymphocyte reaction. The dermal antigen-presentation activities were totally abrogated by removal of class II MHC+ cells, but not by removal of CD11b+ cells or Ly6c+ cells, indicating that potent antigen-presenting cell activity was restricted to the class II MHC+ CD11b- Ly6c- subset (Langerhans cell-like/indeterminant cells). In conclusion, within a complex array of dermal leukocytes a murine dermal class II MHC+ cell population expressing a Langerhans cell-like/dendritic antigen-presenting cell phenotype and exhibiting potent antigen processing and presenting activity can be identified. The positioning of potent interstitial dendritic antigen-presenting cells at the interface of the vasculature with the dermal interstitium provides rapid access to an antigen-presenting cell as T cells first egress into the skin.
真皮细胞能够引发接触性超敏反应，但目前尚缺乏对小鼠真皮内抗原呈递细胞的确切鉴定。在BALB/c和C3H/HeN皮肤的血管周围和间质真皮中观察到具有树突状形态、缺乏内皮因子VIII但表达树突状抗原呈递细胞标志物NLDC-145的II类主要组织相容性复合体（MHC）+细胞。这些异质性的II类MHC+细胞可分为两个亚群：每个亚群均为II类MHC+ CD45+（骨髓来源）GR-1-（非中性粒细胞/巨噬细胞）CD3-（非T细胞），但其中一个亚群为CD11b+（β2整合素），另一个为CD11b-。对II类MHC+细胞的超微结构检查显示存在一个具有核凹陷、树突状形态、活跃细胞质和密集中间丝的朗格汉斯细胞样/不确定细胞亚群。在这些细胞中未观察到吞噬溶酶体和伯贝克颗粒，这表明它们分别与真皮巨噬细胞和经典的表皮朗格汉斯细胞不同。还注意到具有单核细胞/巨噬细胞超微结构外观的细胞，可能代表表达CD11b和Ly6c（单核细胞/内皮抗原）的II类MHC亚群。悬浮的真皮细胞能够处理并将大蛋白抗原呈递给抗原特异性T细胞杂交瘤；真皮细胞还能诱导同基因混合淋巴细胞反应。去除II类MHC+细胞可完全消除真皮的抗原呈递活性，但去除CD11b+细胞或Ly6c+细胞则不能，这表明有效的抗原呈递细胞活性仅限于II类MHC+ CD11b- Ly6c-亚群（朗格汉斯细胞样/不确定细胞）。总之，在复杂的真皮白细胞群体中，可以鉴定出一种表达朗格汉斯细胞样/树突状抗原呈递细胞表型并具有强大抗原加工和呈递活性的小鼠真皮II类MHC+细胞群体。强大的间质树突状抗原呈递细胞位于血管系统与真皮间质的界面处，使得T细胞首次进入皮肤时能够快速接触到抗原呈递细胞。
