Steinman R, Hoffman L, Pope M
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10021, USA.
J Invest Dermatol. 1995 Jul;105(1 Suppl):2S-7S. doi: 10.1111/1523-1747.ep12315162.
Dendritic cells have been isolated from the epidermis, dermis, and lymphatics of skin. Cells from each cutaneous compartment can exhibit the distinct morphology, surface phenotype, and strong T-cell-stimulating activity of dendritic cells that are isolated from other organs. Of importance are the mechanisms by which the maturation and movement of dendritic cells are regulated within intact tissues. Epidermal dendritic cells turn over slowly in the steady state. Stimuli, including contact allergens and transplantation, perhaps by inducing a release of cytokines such as granulocyte macrophage-colony-stimulating factor, mobilize these dendritic cells into the dermis and lymph. This migration is accompanied by the maturation of dendritic cell functions; e.g., antigen-presenting major histocompatibility complex molecules and B7 costimulators increase markedly. On the other hand, there is a sizable, steady-state flux of dendritic cells in afferent lymph draining the skin, which suggests a constant traffic through the dermis that is independent of sessile epidermal dendritic cells. When explants of skin are placed in organ culture, dendritic cells emigrate into the medium for 1-3 d. The dendritic cells are mature and can bind tightly to small memory T cells that also migrate in these cultures. The emigrated mixtures of dendritic cells and T cells should be useful in the study of many clinical states. This is illustrated by recent experiments showing that migratory skin cells are readily infected with human immunodeficiency virus (HIV)-1. A strong productive infection takes place in the absence of exogenous cytokines, foreign sera, or mitogens or antigens. The dendritic cell-T-cell conjugates are the essential site for infection. This cellular milieu may model events during the sexual transmission of HIV-1, where relevant mucosal surfaces are covered by skin-like epithelia. The capture of CD4+ memory T cells by dendritic cells may explain the chronic drain of immune memory in HIV infection.
树突状细胞已从皮肤的表皮、真皮和淋巴管中分离出来。来自皮肤各层的细胞可呈现出与从其他器官分离出的树突状细胞不同的形态、表面表型及强大的T细胞刺激活性。重要的是树突状细胞在完整组织内成熟和移动的调控机制。在稳态下，表皮树突状细胞更新缓慢。包括接触性变应原和移植在内的刺激因素，可能通过诱导粒细胞巨噬细胞集落刺激因子等细胞因子的释放，将这些树突状细胞动员至真皮和淋巴管。这种迁移伴随着树突状细胞功能的成熟，例如抗原呈递主要组织相容性复合体分子和B7共刺激分子显著增加。另一方面，引流皮肤的输入淋巴管中存在大量稳态的树突状细胞流，这表明存在不依赖于固定表皮树突状细胞的恒定真皮穿行。当将皮肤外植体置于器官培养中时，树突状细胞会在1至3天内迁移至培养基中。这些树突状细胞已成熟，并且能紧密结合同样在这些培养物中迁移的小记忆T细胞。树突状细胞和T细胞的迁移混合物在许多临床状态的研究中应会很有用。最近的实验表明迁移的皮肤细胞很容易被人类免疫缺陷病毒1型（HIV-1）感染，这说明了这点。在没有外源性细胞因子、异体血清或促有丝分裂原或抗原的情况下会发生强烈的有效感染。树突状细胞-T细胞结合物是感染的关键部位。这种细胞环境可能模拟HIV-1性传播过程中的事件，相关的黏膜表面被类似皮肤的上皮覆盖。树突状细胞对CD4 +记忆T细胞的捕获可能解释了HIV感染中免疫记忆的慢性消耗。
