[Contact sensitivity reaction, its mechanism and regulation]

The contact sensitivity (CS) reaction to haptens is a classical example of cell-mediated immune response. In this reaction, two phases can be distinguished: an early component, detectable as early as 2 hr after subsequent contact with the hapten, and a late component, developing approximately 24 hr after challenge and which is mediated by T cells. In the classical CS reaction, CD4+ T helper 1 (Th1) cells act as effector cells, whereas B-1 lymphocytes supported by NKT cells produce antigen-specific IgM antibodies, which play a crucial role in the initiation of CS. The CS reaction is under the precise control of regulatory circuits. The CS response is negatively regulated by T suppressor (Ts) cells induced by treatment with high doses of antigen. On the other hand, the CS response is positively regulated by T contrasuppressor (Tcs) cells that protect Th1 effector lymphocytes from the action of Ts cells. A new view of a negative regulation of Th1-mediated CS response is based on suppression induced by epicutaneous (e.c.) application of protein antigen. This kind of immunization results in the generation of TCR alphabeta+CD4+CD8+ Ts cells that inhibit the CS response via the released TGF-beta. The suppression induced via e.c. immunization with protein antigen can be abrogated by TCR alphabeta+CD4+ Tcs cells induced by simultaneous exposure to protein antigen and Toll-like receptor (TLR) ligands. This method of e.c.-induced tolerance or its reversal by e.c. application of antigen alone or together with TLR ligands may be effective in new therapeutic strategies because of its effectiveness, ease of induction, and noninvasiveness.