Immune regulation in allergic and irritant skin reactions.

Contact dermatitis is an inflammatory response ofthe skin characterized by dermal perivascular and epidermal mononuclearjiell infiltration, spongiosis, and hyperplasia. Often a reslilt of insult by antigen or irritant, it is caused by an upset in the normal balance of immunoregulatory signals from both resident and nonresident cells. T cells, which continuously traffic through the skin, are central to the skin's immunoregulation. Their activation and subsequent lymphokine release are critical events in the development of an inflammatory immune reaction. Activation of T lymphocytes can occur via either antigen-dependent or antigen-independent pathways. Antigen-dependent recognition is critical to allergic contact dermatitis reactions, whereas antigen-independent pathways seem important in irritant-induced contact dermatitis. Langerhans cells are the only antigen-presenting cells constitutively found in the epidermis. They present antigen to T cells, thereby eliciting T-cell activation and providing positive signals for upregulation of the immune response. Conversely, other epidermal antigen-presenting cell (APC) subtypes that migrate into the epidermis during an allergic contact dermatitis reaction may activate suppressor pathways, thus downregulating the immune reaction. Keratinocytes, which comprise approximately 90% of the total epidermal cell population, are not passive bystanders in the immune response and can transmit both positive and negative signals. Thus, they may function as a modulator ofthe immune system, upor downregulating T-cell responses. Injuryor irritant-activated keratinocytes can elaborate factors and cytokines that may be responsible for antigen-independent T-cell activation and lymphokine release resulting in