ABSTRACT

The acquisition of skin sensitization is dependent upon the initiation of an immune response and specifi cally a cell-mediated immune response. The relevant events and processes can be summarized briefl y as follows: Sensitization is induced when an inherently susceptible individual is exposed topically to an appropriate and suffi cient amount of contact allergen. Following entry into the skin, the chemical allergen either directly, or indirectly, associates with the protein and is recognized and internalized by cutaneous dendritic cells (DCs) including epidermal Langerhans cells (LCs) and dermal DCs. It is now clear that DCs play several pivotal roles in the generation and regulation of cutaneous immune responses and the induction of skin sensitization. For sensitization, their most important responsibility is the transport of antigen, via the afferent lymphatics, to the draining lymph nodes. During this migration from the skin, DC are subjected to a functional maturation, and as a result, by the time they arrive at the lymph nodes they have acquired the characteristics of the immunostimulatory antigen presenting cells (1,2). In the lymph nodes, the antigen is presented to T lymphocytes and the responsive cells become activated and are stimulated to divide and differentiate. Cell division results in a selective clonal expansion of allergen-responsive T lymphocytes; this quantitative increase in specifi c T lymphocytes represents the cellular basis for sensitization and immunological memory. If the now sensitized subject is exposed again to the same chemical, at the same or a different site, then this expanded population of specifi c T lymphocytes will recognize and respond to the allergen in the skin and trigger an accelerated and more aggressive secondary immune response, which in turn causes cutaneous infl ammation that is recognized clinically as allergic contact dermatitis. The molecular and cellular mechanisms that result in the induction and elicitation of contact allergy have been reviewed extensively elsewhere (3-5). For the purpose of this article it is suffi cient to state that the ability of chemical allergens to stimulate lymph node cell (LNC) proliferative responses is the event upon which the local lymph node assay (LLNA) is founded.