title: Direct Ni2+ antigen formation on cultured human dendritic cells.
abstract: The possible direct antigen formation of Ni2+ on antigen-presenting cells (APCs) was studied with cultured human dendritic cells (DCs) obtained from 10 subjects contact allergic to Ni2+ and six non-allergic control individuals. All contact allergic subjects showed a significantly increased peripheral blood mononuclear cell (PBMC) response in vitro to Ni2+. DCs were expanded from the plastic-adherent cell fraction of PBMCs by culturing with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) for 7 days to obtain immature DCs, and with the addition of monocyte-conditioned medium for another 4 days, for DC maturation. The DCs were pulsed for 20 min with Ni2+ (50 micrometers) in protein-free Hank's balanced salt solution (HBSS) and added to freshly prepared autologous responder PBMCs. With five allergic subjects, immature DCs pulsed with Ni2+ demonstrated a significant capacity to activate Ni2+-reactive lymphocytes. With the remaining five patients and the six controls no difference in lymphocyte proliferation was observed between Ni2+-pulsed and non-pulsed immature DCs. In contrast, with mature Ni2+-pulsed DCs from both 'positive responder' (n=4) and 'non-responder' (n=4) patients, there was a significantly stimulated PBMC proliferation, whereas with the controls (n=4) still no activation was observed. Our results indicate that direct formation of the antigenic determinant of Ni2+ on APCs is possible and that Ni2+ uptake and processing mechanisms may not play a major role. Differences in the ease of activation of Ni2+-reactive lymphocytes are discussed in terms of a possible heterogeneity in the availability of Ni2+-reactive groups presented on endogenous peptides bound in the antigen binding groove of human leucocyte antigen (HLA) class-II molecules.
authors.affiliation: Department of Occupational Medicine, Dermatology Division, National Institute for Working Life; Department of Laboratory Medicine, Division of Clinical Immunology, Karolinska Institute and Hospital, Stockholm, Sweden.
authors.forename: L T
authors.initials: LT
authors.lastname: Van Den Broeke
authors.forename: L C
authors.initials: LC
authors.lastname: Heffler
authors.forename: M
authors.initials: M
authors.lastname: Tengvall Linder
authors.forename: J L
authors.initials: JL
authors.lastname: Nilsson
authors.forename: A T
authors.initials: AT
authors.lastname: Karlberg
authors.forename: A
authors.initials: A
authors.lastname: Scheynius
mesh_terms: D000328:Adult; D017951:Antigen Presentation / Q000276:immunology; D018929:Cell Culture Techniques; D002455:Cell Division / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D009532:Nickel / Q000276:immunology*
chemical_list: D009532:Nickel