REDUCED IL-12 PRODUCTION BY MONOCYTES UPON ULTRAVIOLET-B IRRADIATION SELECTIVELY LIMITS ACTIVATION OF T HELPER-1 CELLS

The capacity of APC to stimulate the proliferation of human peripheral blood T cells decreases upon ultraviolet-B (UVB) irradiation. The aim of this study was to investigate whether all T cell subsets are equal ly sensitive to this reduced APC function. Established human Th1, Th2, and Th0 clones were stimulated with monocytes in a soluble CD3 mAb-me diated assay that is dependent on the presence of APC. Monocytes were exposed to low nonlethal doses of UVB radiation before coculture with T cells. UVB irradiation inhibited the capacity of monocytes to stimul ate the proliferation and IFN-gamma production of Th1 cells in a dose- related fashion, In contrast, UVB-treated monocytes induced normal pro liferation and IL-4 production in Th2 cells. Stimulation of Th0 cell p roliferation by UVB-irradiated monocytes was normal, but a preferentia l suppression of IFN-gamma production was observed, thus leading to a more Th2-like cytokine response. The loss of Th1 proliferation upon st imulation with UVB-irradiated monocytes could be overcome by rIL-2; ho wever, IFN-gamma production remained suppressed, IFN-gamma production could be completely restored by rIL-12, whereas the addition of IL-1 b eta, TNF-alpha, or indomethacin had no such effect, nor did the additi on of mAb to CD28, added to compensate for the reduced B7 expression o f UVB-irradiated monocytes. Monocytes exposed to UVB radiation exhibit ed reduced expression of mRNA for the IL-12 subunits p35 and p40 and s uppressed production of the IL-12 p70 protein. Our results thus indica te that UVB irradiation of APC selectively impairs Th1-like responses, a phenomenon caused by the UVB-induced suppression of monocyte IL-12 production.