Deficient Th1-type immune responses via impaired CD28 signaling in ultraviolet B-induced systemic immunosuppression and the restorative effect of IL-12

A single large dose (15 kJ/m(2)) of UVB-irradiation induces systemic immuno suppression and tolerance. We previously reported that IL-12 promotes the a ccessary cell Function of epidermal Langerhans cells. In this study we have examined whether IL-12-pretreated antigen-presenting cells (APC) could res tore the diminished T-cell response in mice irradiated with a single large dose of UVB. Spleen cells from UVB-irradiated mice showed reduced IFN-gamma production in a hapten-specific response but the function of APC in non-ex posed skin of UVB-irradiated mice was not impaired. The pretreatment of APC with IL-12 did not restore the impaired IFN-gamma production by T cells fr om UVB-irradiated mice. Neither IL-10 nor TGF-beta was found to be involved in the suppression. Instead, we observed that anti-CDS mAb-induced IFN-gam ma production by T cells from UVB-irradiated mice was not augmented in the presence of anti-CD28 mAb, whereas IL-4 production was enhanced by the addi tion of anti-CD28 mAb. Furthermore, the reduced IFN-gamma production by T c ells from UVB-irradiated mice in response to antigen plus APC could be rest ored by adding IL-12 to the culture. Our results thus indicate that UVB-ind uced systemic immunosuppression involves impaired Th1-type responses of T l ymphocytes through CD28 stimulation, and that IL-12 compensates for the imp aired CD28 costimulatory signaling in T tells resulting in the restoration of Th1-type responses. (C) 2000 Elsevier Science Ireland Ltd. All rights re served.