UROCANIC ACID ENHANCES IL-10 PRODUCTION IN ACTIVATED CD4(-CELLS() T)

The immunosuppressive effects of UV radiation have been well documente d, This suppression has been attributed to the action of the cis form of urocanic acid (UCA), a photoproduct of trans-UCA, a natural constit uent of the skin. Here, we show that mouse spleen cells preincubated w ith cis-UCA have a diminished proliferative response to allogeneic cel ls in MLC and to stimulation with anti-CD3 mAb, Cells preincubated wit h cis-UCA also had a decreased ability to serve as APC and to stimulat e the proliferation of allogeneic lymphocytes in MLC, Simultaneously, the,production of IL-2 and IFN-gamma by cells preincubated with cis-UC A was decreased. However, IL-10 gene expression and IL-10 protein secr etion by spleen cells stimulated in the presence of cis-UCA were signi ficantly enhanced. The principal cell population displaying the cis-UC A-induced elevated production of IL-10 mas CD4(+) T cells, which were shown to be a direct target of cis-UCA action. This was also supported by the observation that production of IL-10 by stimulated splenic non -T cells or by macrophages was not altered by cis-UCA. The enhanced pr oduction of IL-10 by activated CD4(+) T cells may represent a novel pa thway of UVB radiation-induced, cis-UCA-mediated immunosuppression. We suggest that the elevated production of IL-10 by activated CD4+ T cel ls may account for the suppressor T cell phenomena described in UV-irr adiated recipients.