Price, Abigail Anne; (1997) The role of adhesion molecules in the migration of Langerhans cells. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Dendritic cells (DC) are potent antigen presenting cells that are located in virtually all tissues of the body. The DC of the skin are called Langerhans cells (LC), which, upon exposure to antigen, migrate to draining lymph nodes where they accumulate as lymphoid DC. During migration LC mature and acquire the ability to initiate immune responses by presenting antigen to naive T lymphocytes. The migration of other types of leucocyte is mediated by cell adhesion molecules, however, the adhesion molecules that regulate LC migration from the skin to the draining lymph nodes are poorly defined. The aim of this study is to examine the role of adhesion molecules in regulating LC migration in BALB/c mice. Flow cytometric and immunohistochemical examination of LC and lymph node DC revealed differential expression of several adhesion molecules; LC expressed low levels of α4 integrin and a proportion (60–70%) expressed high levels of α6 integrin. In contrast, DC did not express detectable levels of α6 integrin, but expressed high levels of α4 integrin. The importance of these integrins, and other adhesion molecules, for LC migration was investigated in vitro, using a skin explant model of LC migration; LC migrate out of cultured skin over a 3 day period. Addition of antibodies to integrin, but not to α4 integrin, to the culture medium significantly reduced the number of LC that migrated from the epidermis. To determine whether α6 integrin or α4 integrin is important for LC migration to the draining lymph nodes in vivo , antibodies to these integrins were administered systemically, two hours prior to topical exposure to the skin sensitizer, oxazolone. Antibodies to α6 integrin, but not to α4 integrin significantly reduced DC accumulation in draining lymph nodes 18 hours after exposure to oxazolone. Taken together, these results suggest that α6 integrin-ligand interactions are required for LC migration.

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