Antigen-bearing dendritic cells in the draining lymph nodes of contact sensitized mice: cluster formation with lymphocytes

Abstract

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.