title: Inhibition of Langerhans cell antigen-presenting function by IL-10. A role for IL-10 in induction of tolerance.
abstract: IL-10 is a product of activated keratinocytes and is released during the induction phase of contact sensitivity. As IL-10 effects have been described as being mediated by APC, we investigated effects of IL-10 on epidermal Langerhans cells (LC), the resident APC in the epidermis. Initial studies failed to demonstrate effects of IL-10 on MHC class II Ag expression by LC or anti-CD3 mAb- or alloantigen-induced LC-dependent T cell proliferation. However, production of IFN-gamma and IL-2, (but not IL-6) was markedly reduced in these assays. When the soluble-protein Ag specific T cell clones AE7 (Th1) and D10.G4 (Th2) were substituted for unprimed T cells, differential effects of IL-10 on T-cell proliferation were observed. Whereas IL-10-pretreated and untreated LC supported Th2 cell proliferation equally well, IL-10-pretreated LC were essentially unable to induce Th1 cell proliferation in response to native protein or peptide Ag. The inhibitory influence of IL-10 on Th1 cells was observed when fresh or 1 day cultured LC were used; 2- or 3-day cultured LC were affected to a much lesser extent by IL-10 pretreatment. Further, coculture experiments using IL-10-pretreated or untreated LC of a different haplotype suggest that IL-10 negatively regulates a costimulatory signal required for induction of Th1 cell proliferation. To assess whether T cells incubated with Ag and IL-10-pretreated LC were responsive to further stimulation, T cells were rescued after 1 day of coculture with IL-10-pretreated LC and restimulated, either immediately or after 1 to 5 days of rest, with untreated LC in the presence of Ag. T cells incubated with IL-10-pretreated LC were found to be anergic, whereas T cells incubated with untreated LC proliferated normally after further stimulation. However, anergic T cells responded vigorously to IL-2. These data indicate that although IL-10-pretreated LC are effective APC for Th2 cells, they fail to induce Th1 cell proliferation and rather induce clonal anergy in these cells.
authors.affiliation: Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: A H
authors.initials: AH
authors.lastname: Enk
authors.forename: V L
authors.initials: VL
authors.lastname: Angeloni
authors.forename: M C
authors.initials: MC
authors.lastname: Udey
authors.forename: S I
authors.initials: SI
authors.lastname: Katz
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects*; D017252:CD3 Complex / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007108:Immune Tolerance / Q000187:drug effects*; D016753:Interleukin-10 / Q000494:pharmacology*; D007801:Langerhans Cells / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D017252:CD3 Complex; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D016753:Interleukin-10