Workshops

Delayed type hypersensitivity reactions (DTHR) normally protect against infectious diseases. Whoever when directed against autoantigens they may induce organ specific auto-immune diseases such as multiple sclerosis, autoimmune arthritis, diabetes or psoriasis and, when directed to haptens on the skin, contact hypersensitivity (CHS). These diseases affect more than 10% of the population in industrialized countries. In mice, DTHR may frequently be prevented by deviation of interferon g (IFNg) producing T cells (Thl) to interleukin 4 (IL-4) producing T cells (Th2) during the initial activation of the T cells. However, memory Thl responses are considered to be stable and can only be controlled by conventional immunosuppression. In vitro evidence showing that the lymphokine phenotype of immune responses may retain some plasticity led us to investigate therapeutic immune deviation of already established DTHR in vivo, using CHS as a model. During DTHR, such as CHS, proinflammatory Thl cytokines dominate the early phases of the reactions and Th2 cytokines the late phases. This observation suggests that Thl initiate and that Th2 terminate DTHR. So far it was only possible to aggravate or suppress the effector phase of DTHR by IL-12 or anti-lL-4 and ameliorate DTHR by IL-4. We now show that established DTHR can not only be suppressed by IL-4 but also be efficiently treated with hapten and IL-4. This therapeutic immune deviation with IL-4 and hapten of firmly established CHS induced a novel state of reactivity. Subsequent hapten exposures resulted in an unusually early IL-4 expression, 4-6 hours after hapten reexposure. Neutrophil recruitment, tissue swelling and tissue destruction were strqngly reduced, despite unchanged expression of Thl cytokines. The therapy was ineffective in IL-4.ko mice. Thus, the dynamics of IL-4 expression are sensitive to therapeutic strategies and may ultimately determine the course of DTHR. and autoimmune dermatoses