Allergic contact dermatitis can be caused by the activation of CD4 or CD8 T cells, depending on the pathway by which the antigen is processed. Typical antigens that cause allergic contact dermatitis are highly reactive small molecules that can easily penetrate intact skin, especially if they cause itching that leads to scratching and its consequent injury to the skin barrier. These chemicals then react with self proteins, creating haptenated proteins that can be proteolytically processed in antigen-presenting cells to haptenated peptides capable of being presented by MHC molecules and recognized by T cells as foreign antigens. As with other allergic responses, there are two phases to a cutaneous allergic response: sensitization and elicitation. During the sensitization phase, Langerhans cells in the epidermis and dendritic cells in the dermis take up and process antigen, and migrate to regional lymph nodes, where they activate T cells (see Fig. 9.13) with the consequent production of memory T cells, which localize in the dermis. In the elicitation phase, a subsequent exposure to the sensitizing chemical leads to antigen presentation to memory T cells in the dermis, with the release of T-cell cytokines such as IFN-γ and IL-17. This stimulates the keratinocytes of the epidermis to release IL-1, IL-6, TNF-α, GM-CSF, the chemokine CXCL8, and the interferon-inducible chemokines CXCL11 (IP-9), CXCL10 (IP-10), and CXCL9 (Mig, a monokine induced by IFN-γ). These cytokines and chemokines enhance the inflammatory response by inducing the migration of monocytes into the lesion and their maturation into macrophages, and by attracting more T cells (Fig. 14.22).
The rash produced by contact with the poison ivy plant (Fig. 14.23) is a common example of allergic contact dermatitis in the United States and is caused by a CD8 T-cell response to urushiol oil (a mixture of pentadecacatechols) in the plant. These chemicals are lipid-soluble and so can cross the cell membrane and attach to intracellular proteins. The modified proteins are recognized by the immunoproteasome, and following cleavage, they are translocated into the endoplasmic reticulum and delivered to the cell surface bound to MHC class I molecules. CD8 T cells recognizing the peptides cause damage either by killing the eliciting cell or by secreting cytokines such as IFN-γ.
Fig. 14.22 Elicitation of a delayed-type hypersensitivity TH1 cells (which were primed in lymph nodes as a result of prior response to a contact-sensitizing agent. A contact-sensitizing antigen exposure). The activated TH1 cells then secrete cytokines agent is a small, highly reactive molecule that can penetrate intact such as IFN-γ that stimulate keratinocytes to secrete additional skin. It binds covalently as a hapten to a variety of endogenous cytokines and chemokines, which in turn attract monocytes and proteins, altering their structures so they become antigenic. These induce their maturation into activated tissue macrophages, further modified proteins are internalized, processed by Langerhans cells contributing to inflammatory lesions like those caused by poison ivy (the major antigen-presenting cells of skin), and presented to effector (see Fig. 14.23). NO, nitric oxide.