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Direct Ni 2+ antigen formation on cultured human dendritic cells
Author(s) -
Leon T. van den Broeke,
Lena C. Heffler,
Maria Tengvall Linder,
Jonas Nilsson,
Karlberg At,
Annika Scheynius
Publication year - 1999
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1999.00739.x
Subject(s) - peripheral blood mononuclear cell , antigen , dendritic cell , immunology , monocyte , in vitro , chemistry , t lymphocyte , microbiology and biotechnology , biology , biochemistry
The possible direct antigen formation of Ni 2+ on antigen‐presenting cells (APCs) was studied with cultured human dendritic cells (DCs) obtained from 10 subjects contact allergic to Ni 2+ and six non‐allergic control individuals. All contact allergic subjects showed a significantly increased peripheral blood mononuclear cell (PBMC) response in vitro to Ni 2+ . 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 Ni 2+ (50 μm) 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 Ni 2+ demonstrated a significant capacity to activate Ni 2+ ‐reactive lymphocytes. With the remaining five patients and the six controls no difference in lymphocyte proliferation was observed between Ni 2+ ‐pulsed and non‐pulsed immature DCs. In contrast, with mature Ni 2+ ‐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 Ni 2+ on APCs is possible and that Ni 2+ uptake and processing mechanisms may not play a major role. Differences in the ease of activation of Ni 2+ ‐reactive lymphocytes are discussed in terms of a possible heterogeneity in the availability of Ni 2+ ‐reactive groups presented on endogenous peptides bound in the antigen binding groove of human leucocyte antigen (HLA) class‐II molecules.