Migration and maturation of Langerhans cells in skin transplants and explants.
Migration and maturation of Langerhans cells in skin transplants and explants.
复制标题
皮肤移植和外植体中Langerhans细胞的迁移和成熟。
DOI：
10.1084/jem.172.5.1483
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发表时间：
1990-11-01
影响因子：
15.3
通讯作者：
Austyn, J M
中科院分区：
文献类型：
--
作者：
Larsen, C P;Steinman, R M;Witmer-Pack, M;Hankins, D F;Morris, P J;Austyn, J M
郎格罕细胞（LC）的行为已被检查后，皮肤移植和器官培养系统。在24小时内（甚至在4小时内的文化），LC在表皮片从同种异体移植物，同种异体移植物，外植体的大小和主要组织相容性复合体II类分子的表达显着增加，其数量显着减少。使用一种新的程序，然后检查真皮片。24 h时，在表皮-真皮交界处发现了类似LC的细胞，3 d时，它们在离开皮肤前在真皮层形成索状。在器官培养中，细胞继续自发迁移到培养基中。这些观察结果建立了LC从表皮迁移到真皮然后从皮肤中迁移的直接途径。这些过程显然是由局部炎症反应诱导的，并且不依赖于宿主来源的介质。然后通过双色免疫细胞化学和流式细胞仪分析检测迁移细胞的表型。大多数迁移性白细胞为Ia+ LC，其余包括Thy-1+、CD 3+、CD 4-、CD 8-推定T细胞受体γ/δ +树突状表皮细胞，其与LC聚集，以及少量粘附的Ia-、FcRII+、CD 11 a/18+巨噬细胞。相反，在1天的移植皮肤的表皮内保留的细胞，迁移细胞的表型是异质性的，特别是相对于F4/80，FcRII，白细胞介素2受体α的表达，这是有用的标记，遵循LC的表型成熟。此外，从移植物的表皮分离的细胞在第1天的异基因混合白细胞反应和氧化有丝分裂比LC从正常皮肤中分离的免疫刺激，虽然不如脾细胞。第1天的迁移细胞比脾细胞具有更强的免疫刺激性，第3-5天的迁移细胞更是如此，这表明功能成熟在培养中继续。因此，LC的成熟在表皮中开始并在迁移期间继续，但细胞在离开皮肤之前不需要在表型或功能上完全成熟。在体内，表皮LC通过真皮迁移到淋巴结，然后迁移到引流结，在那里它们已经被证明是T区的归宿，这将为移植物排斥提供强大的刺激。
The behavior of Langerhans cells (LC) has been examined after skin transplantation and in an organ culture system. Within 24 h (and even within 4 h of culture), LC in epidermal sheets from allografts, isografts, and explants dramatically increased in size and expression of major histocompatibility complex class II molecules, and their numbers were markedly decreased. Using a new procedure, dermal sheets were then examined. By 24 h, cells resembling LC were found close to the epidermal-dermal junction, and by 3 d, they formed cords in dermal lymphatics before leaving the skin. In organ culture, the cells continued to migrate spontaneously into the medium. These observations establish a direct route for migration of LC from the epidermis into the dermis and then out of the skin. These processes are apparently induced by a local inflammatory response, and are independent of host- derived mediators. The phenotype of migratory cells was then examined by two-color immunocytochemistry and FACS analysis. The majority of migratory leukocytes were Ia+ LC, the remainder comprised Thy-1+, CD3+, CD4-, CD8- presumptive T cell receptor gamma/delta+ dendritic epidermal cells, which clustered with the LC, and a small population of adherent Ia-, FcRII+, CD11a/18+ macrophages. In contrast to the cells remaining within the epidermis of grafted skin at 1 d, the migratory cells were heterogeneous in phenotype, particularly with respect to F4/80, FcRII, and interleukin 2 receptor alpha expression, which are useful markers to follow phenotypic maturation of LC. Moreover, cells isolated from the epidermis of grafts at 1 d were more immunostimulatory in the allogeneic mixed leukocyte reaction and oxidative mitogenesis than LC isolated from normal skin, though less potent than spleen cells. The day 1 migratory cells were considerably more immunostimulatory than spleen cells, and day 3-5 migratory cells even more so, suggesting that functional maturation continues in culture. Thus, maturation of LC commences in the epidermis and continues during migration, but the cells do not need to be fully mature in phenotype or function before they leave the skin. In vivo, the migration of epidermal LC via the dermis into lymphatics and then to the draining nodes, where they have been shown previously to home to T areas, would provide a powerful stimulus for graft rejection.