Immunological Mechanisms in Allergic Contact Dermatitis

Purpose of the review: The understanding of the cellular and molecular pathogenesis of allergic contact dermatitis (ACD) has increased dramatically. Recent findings: Besides CD4+ and CD8+ T cells, other cell types such as innate lymphoid cells, natural killer T cells (NKT), natural killer cells, and T regulatory cells have emerged as crucial key players. New immunological insights have unravelled that the predominant effector cell type determines the clinical pictures. Hence, a better understanding of the involvement of distinct effector cells has shed light on the diversity of ACD reactions and subsequent clinical pictures. Another new perspective has arisen in the elicitation phase. Here, Langerhans cells can play a role in the development of immune tolerance and not, as previously thought, exclusively in the allergen-driven hypersensitivity reaction. B cells also appear to play an important role in triggering ACD by secreting IgM antibodies in response to interleukin (IL)-4 produced by NKT cells, leading to complement activation and chemotaxis of immune cells. Summary: Allergic contact dermatitis is a delayed-type hypersensitivity reaction triggered by skin contact with the chemical of interest in individuals previously sensitised to the same or a chemically related substance. The understanding of the cellular and molecular pathogenesis of allergic contact dermatitis has improved considerably. In addition to CD4+ and CD8+ T cells, other cell types such as natural killer T cells (NKT) and regulatory T cells have emerged as important participants. The binding of haptens is the first step in the development of allergic contact dermatitis. Haptens are low molecular weight (mostly <500 Dalton) chemicals that are able to penetrate the stratum corneum of the skin or can enter the body upon systemic administration. Haptens are not immunogenic per se but can be effectively recognised by the immune system after binding to a protein carrier. In the clinically inapparent sensitisation phase, Langerhans cells and dendritic cells initiate an adaptive immune response by capturing and processing antigens and presenting them to naïve T cells in the paracortical regions of the lymph nodes. In the elicitation phase, the clinical manifestations of allergic contact dermatitis are the result of a T cell-mediated inflammatory response that occurs in the skin upon re-exposure to the bite and is mediated by the activation of bite-specific T cells in the skin or other organs.