PSORIATIC SKIN-DERIVED DENDRITIC CELL-FUNCTION IS INHIBITED BY EXOGENOUS IL-10 DIFFERENTIAL MODULATION OF B7-1 (CD80) AND B7-2 (CD86) EXPRESSION

Regulation of immune responses depends on interactions between APCs an d T cells. Such cellular interactions are mediated by surface molecule s including MHC class II Ags (DR) and CD28 ligands B7-1 (CD80) and B7- 2 (CD86). Recent evidence indicates that the presence or absence of co stimulatory molecules on APCs significantly influences the qualitative and quantitative nature of an immune response. In this report, we ana lyze two relevant cytokines in skin immunobiology, granulocyte-macroph age (GM)-CSF and IL-10, and demonstrate their effects on cultured dend ritic cells obtained from dermis (DDCs) of normal skin and psoriatic l esions. For comparison, the effects on these professional APCs were co ntrasted with cultured blood-derived monocytes. Normal and psoriatic s kin-derived DDCs express high levels of CD86 over CD80, and the overal l hierarchy is DR > CD86 > CD80, whereas cultured monocytes express lo w and equivalent levels of CD80 and CD86. If Ab is added to GM-CSF at the initial period of cultivation, DDCs that emigrate have lower level s of CD86 without any detectable effect on CD80 or DR expression and d isplay a reduced capacity to stimulate either superantigen-driven or a lloantigen-responsive T cells. Conversely, by adding GM-CSF to monocyt es, CD86 levels are enhanced. When IL-10 was added at the beginning of culture, DDCs had significantly lower levels of CD86, without any eff ect on CD80 or DR expression, and like anti-GM-CSF-treated cells, thes e DDCs had approximately a 50% reduction in their T cell-stimulating c apacity. In contrast, when monocytes were treated identically with exo genously added IL-10, they retained their relatively low levels of CD8 0 and CD86 with no detectable change in APC function. Blocking studies of DDC:T cell interaction indicated that CD86 was more important than CD80. Thus, differential expression patterns and functional cytokine responses involving these APC populations may be relevant to skin diso rders such as psoriasis, in which discordant patterns of CD28 ligand e xpression and disordered cytokine networks are present.