Allergic Contact Dermatitis

Abstract

Allergic contact dermatitis is a classic example of a cell mediated hypersensitivity reaction in the skin. This occurs as a result of xenobiotic chemicals penetrating into the skin, chemically reacting with self proteins, eventually resulting in a hapten-specific immune response. It is precisely because of this localized immune response that allergic signs and symptoms occur (redness, edema, warmth and pruritus). It has been known for years that conventional T-cells (CD4+ or CD8+ T-cells that express a T-cell receptor alpha/Beta) are critical effectors for this reaction. There is emerging evidence that innate immune lymphocytes such as invariant Natural killer T-cells and even Natural killer cells may play important role. Other T-cell types such as Tregulatory cells and the IL-10 secreting Tregulatory cells type I are likely to be important in the control (resolution) of allergic contact dermatitis. Other cell types that may contribute include B-cells and hapten-specific IgM. Additionally, epidermal Langerhans cells have been ascribed an indispensable role as an antigen presenting cell to educate T-cells of the skin immune system. Studies of mice that lack this cell type suggest that Langerhans cells may be dispensible, and may even play a regulatory role in allergic contact dermatitis. The identity of the antigen presenting cells that complement Langerhans cells has yet to be identified. Lastly, Keratinocytes play a role in all phases of allergic contact dermatitis, from the early initiation phase with the elaboration of inflammatory cytokines, that plays a role in Langerhans cell migration, and T-cell trafficking, through the height of the inflammatory phase with direct interactions with epidermotrophic T-cells, through the resolution phase of allergic contact dermatitis with the production of anti-inflammatory cytokines and tolerogenic antigen presentation to effector T-cells. As the understanding of allergic contact dermatitis continues to improve, this will provide novel therapeutic targets for immune modulating therapy.

Mechanisms of IL-12 Synthesis by Human Dendritic Cells Treated with the Chemical Sensitizer NiSO4

“…Allergic contact dermatitis (ACD) caused by metallic ions and other reactive haptens is a T cell-mediated inflammatory skin disease (4)(5)(6). ACD is characterized by two phases: a sensitization phase and an elicitation phase.…”

“…IL-12 is primarily produced by macrophages and DCs mainly in response to danger signals such as TLR agonists and plays a major role in IFN-g production by immune cells, driving a Th1/Tc1-type response (13)(14)(15)(16). Many authors have demonstrated that CD8 + cytotoxic T lymphocytes are the main effector cells of ACD and observed their early recruitment in the skin postchallenge with chemical sensitizers (6,17). Injection of IL-12 during the sensitization phase favors CD8 + T cell differentiation and increases the ACD reaction (18).…”

Imunopatologia da dermatite de contato alérgica

“…Under normal conditions, keratinocytes express low levels of the costimulatory molecules CD80 and CD86. 19 These molecules bind to their receptors in T cells (CD28/CTLA-4 -cytotoxic TL-associated antigen-4) and are necessary for leading to a second effective signal. 19 In the absence of a second signal, the TL become anergic.…”

“…19 These molecules bind to their receptors in T cells (CD28/CTLA-4 -cytotoxic TL-associated antigen-4) and are necessary for leading to a second effective signal. 19 In the absence of a second signal, the TL become anergic. 127.128 These anergic TL express a large amount of IL-2 receptors and therefore compete with effector and memory T cells for this growth factor.…”

“…Despite presenting T-cell receptor, these cells do not undergo gene rearrangement and are able to connect, through this TCR, to highly conserved glycolipid bound to CD1d molecules, a molecule similar to MHC class I molecule, which is found in antigen-presenting cells. 19,147,148 The nature of this glycolipid remains unknown. After contact with this glycolipid, the NK T cell proliferates in the liver and releases cytokines such as IL-4, which is responsible for activating type 1 BL in the presence of the antigen.…”