title: Evaluation of the capacity of dendritic cells derived from cord blood CD34+ precursors to present haptens to unsensitized autologous T cells in vitro.
abstract: Langerhans cells play a key role in contact hypersensitivity reactions. The application of haptens on the skin leads to many modifications of these cells, including the increase of major histocompatibility complex II expression, allogeneic stimulation potency, and migration towards lymph nodes to activate T cells. Moreover, it has been shown that Langerhans cells cultured in vitro are able to prime naive T cells in response to hapten contact. From CD34+ progenitors present in cord blood, we generated dendritic cells of which some presented the phenotypic markers of Langerhans cells. We show that these cells are able to sensitize syngeneic naive (CD45RA+) T cells to haptens such as trinitrophenyl conjugate of trinitrobenzene sulfonic acid (TNP) and fluoroscein isothiocyanate. The response to TNP is higher than to fluoroscein isothiocyanate, whereas sodium dodecyl sulfate, an irritant molecule used as a control, never caused this effect. Phenotypic analysis of cellular suspensions and experiments of cell sorting lead to the conclusion that only CD1a+ cells are able to induce a primary response of syngeneic T cells to TNP or fluoroscein isothiocyanate. Furthermore, we have shown a close relationship between the differentiation state of dendritic cells and their ability to prime T lymphocytes. Dendritic cells are able to present haptens in an efficient manner between day 10 and 14 of culturing CD34+ progenitors, whereas they were efficient in presenting alloantigens from day 6 until after day 20. This dissociation suggests the need of an active metabolic process for hapten presentation in the direct treatment of dendritic cells with haptens. This model of hapten presentation was used for a panel of fragrance molecules and other molecules considered as weaker haptens than TNP and fluoroscein isothiocyanate.
authors.affiliation: INSERM, Laboratoire de Recherche Peau Humaine et Immunité, Hôpital Edouard Herriot, Lyon, France.
authors.forename: N
authors.initials: N
authors.lastname: Rougier
authors.forename: G
authors.initials: G
authors.lastname: Redziniak
authors.forename: D
authors.initials: D
authors.lastname: Schmitt
authors.forename: C
authors.initials: C
authors.lastname: Vincent
mesh_terms: D018949:Antigens, CD1 / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis*; D001773:Blood Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005312:Fetal Blood / Q000166:cytology; D016650:Fluorescein-5-isothiocyanate / Q000494:pharmacology; D006241:Haptens / Q000276:immunology*; D006801:Humans; D007114:Immunization; D008213:Lymphocyte Activation / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology
chemical_list: D018949:Antigens, CD1; D018952:Antigens, CD34; D006241:Haptens; D014302:Trinitrobenzenesulfonic Acid; D016650:Fluorescein-5-isothiocyanate