[Contact allergy]

Abstract

Following epicutaneous application of a potential contact sensitizing agent (hapten) allergic contact dermatitis results if sensitizing rather than tolerizing signals become dominant. Whereas downregulatory signals are poorly defined it has become clear that epidermal Langerhans cells play an important role in the induction of contact allergy. The current hypothesis is that in vivo, subsequent to deposition of antigen, resident Langerhans cells mature into potent immunostimulatory, antigen-carrying dendritic cells which migrate via the afferent lymphatics and after their arrival in the draining lymph node select and sensitize clones of antigen-specific T-cells from the circulating pool. These T-cells produce Interleukin-2 and Interferon-gamma, and, thus, constitute so-called type 1 helper T-cells (Th 1). Recent progress has shed light on some major unknowns in this sequence of events such as regulatory influences, nature of the T-cell receptor ligand, and extravasation of T-cells at the site of hapten deposition. For example, epidermal cell-derived cytokines seem important for initiation (Interleukin-1) and sustenance (GM-CSF) of the induction phase. Hapten-specific T-cells seem to see hapten molecules bound to peptides in the groove of the MHC molecules, and specific endothelial adhesion molecules (ELAM-1) mediate extravasation of skin-homing T-cells that carry a specific ligand (CLA). The recent development of techniques to grow murine as well as human Langerhans cells and dendritic cells in large numbers will allow researchers to further elucidate the pathogenesis of contact hypersensitivity and will ultimately lead to the design of novel strategies for immodulation and tolerance induction.