Cumberbatch M, Illingworth I, Kimber I
ICI Central Toxicology Laboratory, Macclesfield, Cheshire, U.K.
Immunology. 1991 Sep;74(1):139-45.
Following topical exposure to skin-sensitizing chemicals, Langerhans' cells, a significant proportion of which bear antigen, are induced to migrate from the epidermis to the regional lymph node. There is evidence that the antigen-bearing cells which arrive in the draining lymph nodes have the functional characteristics of mature dendritic cells (DC) and efficiently induce T-lymphocyte activation in vitro and contact sensitization in vivo. In contrast, freshly isolated Langerhans' cells are known to be relatively inefficient antigen-presenting cells. Evidence exists that during culture in the presence of granulocyte/macrophage colony-stimulating factor, Langerhans' cells undergo a functional maturation and assume the characteristics of dendritic cells. We have speculated that, in response to chemical exposure and the stimulus to migrate. Langerhans' cells undergo a similar maturation in vivo. To investigate this we have examined the capacity of draining lymph node DC to form antigen-independent clusters with T lymphocytes. Previous studies have confirmed that freshly isolated Langerhans' cells are unable to form such clusters. We report, however, that the antigen-bearing DC which arrive in the draining lymph nodes following skin sensitization, and which are recently derived from epidermal Langerhans' cells, efficiently form clusters with lymphocytes. Thus, antigen-bearing DC were found to have formed clusters with lymphocytes in situ in the draining lymph node, and to readily form clusters with lymphocytes in vitro. In both cases a higher proportion of lymphocytes associated with DC in clusters were T cells. An interesting observation was that DC within draining nodes appeared more efficient at cluster formation than DC in resting nodes, and that within draining nodes antigen-bearing DC formed clusters with greater affinity and/or greater stability than DC which lacked antigen. Taken together these data demonstrate that Langerhans' cell-derived antigen-bearing cells which accumulate in the draining lymph nodes following skin sensitization form clusters with lymphocytes in the manner of mature DC. This is compatible with the hypothesis that, while in transit from the skin, Langerhans' cells are subject to a functional maturation comparable to that witnessed in vitro.
在皮肤接触致敏化学物质后,朗格汉斯细胞(其中很大一部分携带抗原)被诱导从表皮迁移至局部淋巴结。有证据表明,到达引流淋巴结的携带抗原的细胞具有成熟树突状细胞(DC)的功能特性,并且在体外能有效诱导T淋巴细胞活化,在体内能引发接触性致敏。相比之下,已知新鲜分离的朗格汉斯细胞是相对低效的抗原呈递细胞。有证据表明,在粒细胞/巨噬细胞集落刺激因子存在的情况下进行培养时,朗格汉斯细胞会经历功能成熟并呈现树突状细胞的特征。我们推测,响应化学物质暴露和迁移刺激,朗格汉斯细胞在体内会经历类似的成熟过程。为了对此进行研究,我们检测了引流淋巴结DC与T淋巴细胞形成不依赖抗原的簇的能力。先前的研究已证实,新鲜分离的朗格汉斯细胞无法形成此类簇。然而,我们报告称,皮肤致敏后到达引流淋巴结的携带抗原的DC,它们最近源自表皮朗格汉斯细胞,能有效地与淋巴细胞形成簇。因此,发现携带抗原的DC在引流淋巴结中与淋巴细胞原位形成了簇,并且在体外很容易与淋巴细胞形成簇。在这两种情况下,与DC形成簇相关的淋巴细胞中T细胞的比例更高。一个有趣的观察结果是,引流淋巴结内的DC在形成簇方面似乎比静止淋巴结中的DC更有效,并且在引流淋巴结内,携带抗原的DC比缺乏抗原的DC以更高的亲和力和/或更高的稳定性形成簇。综合这些数据表明,皮肤致敏后在引流淋巴结中积累的源自朗格汉斯细胞的携带抗原的细胞以成熟DC的方式与淋巴细胞形成簇。这与以下假设相符:在从皮肤迁移的过程中,朗格汉斯细胞会经历与体外所见相当的功能成熟。