The immunology of allergic contact dermatitis: the DNCB story

The observations described here reveal several important aspects of the human immune system and its responses. The immune system is like most major physiologic systems in that it has tidy and predictable dose-response relationships. This applies both to the induction phase and also the elicitation or expression phase. There is thus a graded, dose-related increase in the magnitude of sensitization that applies throughout the range both of clinically detectable reactivity but also down to subclinical levels of response. It becomes possible to speculate about the kinetics of clonal expansion and the stage of the process at which specific T cells leave the lymph node to enter the circulation--the onset of clinical sensitivity. Additional stimulation to the system causes "boosting"--additional clonal expansion, already well known in the field of humoral immunology. Immune responsiveness appears to be normally distributed in the population, with one "tail" of the distribution containing "high responders" who are particularly susceptible to sensitization by environmental antigens. The high responder status reflects a propensity for increased activation of antigen-specific T cells during the induction of the response. Interestingly, the slope of the challenge dose-response curve and hence the expression phase is the same as that for normal subjects. An important factor in the activation or induction of an immune response is the concentration of antigen per unit area. Our studies on the influence of area of application of antigen indicate that at very small areas, between 3 mm and 1 cm across, changing area and hence number of antigen-bearing Langerhans cells may alter sensitization. Above a threshold or plateau level, changing the area makes very little difference, whereas change in the concentration per unit area, i.e., the number of antigen molecules per Langerhans cells, is a powerful determinant of sensitizing potency. We have not explored the upper limit of this phenomenon, i.e., maybe the relationship does not hold above a certain area or dose. The final series of observations showed that the application of antigen to skin pretreated with UVB or PUVA is followed by an absence of immunologic response. This state differs from that seen in mice in that it reflects a "failure" of activation of the immune system rather than a state of down-regulation or tolerance. Having established these ground rules, it will be possible to move on to a whole series of additional questions relating basic aspects of immunology to the applied areas of contact dermatitis.