Immunoregulatory mechanisms involved in elicitation of allergic contact hypersensitivity

At first sight, the pathophysiology of contact hypersensitivity (CHS) seems to be well understood. Whereas this may apply to some extent to the sensitization phase of CHS, very little is actually known about the elicitation phase of this response. Although the mechanisms of T-cell priming (sensitization) may be more interesting for immunologists, those involved in the elicitation of T cell-mediated secondary responses are more relevant for clinical management because clinically manifest allergic contact dermatitis always reflects the effector phase of CHS. This review summarizes the role of different cellular components and soluble mediators on the elicitation of CHS. In addition, recent studies revealed that, besides selective activation of antigen-specific T cells, epicutaneous application of haptens has a number of direct effects on the cutaneous immune system. The most relevant of these are induction of cytokine and chemokine secretion and endothelial activation. In an attempt to integrate data on this issue, it is proposed that the capacity of contact allergens to directly induce proinflammatory signals in the skin is of relevance and perhaps essential for elicitation of clinically manifest CHS responses. Moreover, the proinflammatory effect of allergens themselves may explain the strict dose dependency of CHS responses and the relatively high concentrations of allergens needed for elicitation of CHS because allergens evoke nonspecific irritation only when applied in relatively concentrated form.