title: Psoriatic skin-derived dendritic cell function is inhibited by exogenous IL-10. Differential modulation of B7-1 (CD80) and B7-2 (CD86) expression.
abstract: Regulation of immune responses depends on interactions between APCs and T cells. Such cellular interactions are mediated by surface molecules 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 costimulatory molecules on APCs significantly influences the qualitative and quantitative nature of an immune response. In this report, we analyze two relevant cytokines in skin immunobiology, granulocyte-macrophage (GM)-CSF and IL-10, and demonstrate their effects on cultured dendritic cells obtained from dermis (DDCs) of normal skin and psoriatic lesions. For comparison, the effects on these professional APCs were contrasted with cultured blood-derived monocytes. Normal and psoriatic skin-derived DDCs express high levels of CD86 over CD80, and the overall hierarchy is DR > CD86 > CD80, whereas cultured monocytes express low 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 levels of CD86 without any detectable effect on CD80 or DR expression and display a reduced capacity to stimulate either superantigen-driven or alloantigen-responsive T cells. Conversely, by adding GM-CSF to monocytes, CD86 levels are enhanced. When IL-10 was added at the beginning of culture, DDCs had significantly lower levels of CD86, without any effect on CD80 or DR expression, and like anti-GM-CSF-treated cells, these DDCs had approximately a 50% reduction in their T cell-stimulating capacity. In contrast, when monocytes were treated identically with exogenously added IL-10, they retained their relatively low levels of CD80 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 disorders such as psoriasis, in which discordant patterns of CD28 ligand expression and disordered cytokine networks are present.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor 48109.
authors.forename: R S
authors.initials: RS
authors.lastname: Mitra
authors.forename: T A
authors.initials: TA
authors.lastname: Judge
authors.forename: F O
authors.initials: FO
authors.lastname: Nestle
authors.forename: L A
authors.initials: LA
authors.lastname: Turka
authors.forename: B J
authors.initials: BJ
authors.lastname: Nickoloff
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology*; D051940:B7-2 Antigen; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques; D016753:Interleukin-10 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology*; D011565:Psoriasis / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction / Q000276:immunology; D012867:Skin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D008562:Membrane Glycoproteins; D016753:Interleukin-10; D016178:Granulocyte-Macrophage Colony-Stimulating Factor