title: Relevance of DC-SIGN in DC-induced T cell proliferation.
abstract: The role of dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) in DC-T cell communication was assessed by analyzing the effect of DC-SIGN-blocking mAb in MLR. The results show that the degree of inhibition by DC-SIGN and LFA-1 mAb depends on the magnitude of the MLR and the maturation status of the DC. Addition of DC-SIGN mAb at several time-points during MLR showed that DC-SIGN is involved early on in DC-T cell contacts. This initial role is masked by strong adhesive and costimulatory mechanisms, indicating a short-lived effect of DC-SIGN in DC-T cell interactions. To examine this concept in more detail, the percentage of PBL capable of binding DC-SIGN was determined. Analysis of several donors revealed that 1-20% PBL bind to beads coated with recombinant DC-SIGN, and the DC-SIGN-binding cells comprised all major cell subsets found in blood. PBL isolated from a donor with high DC-SIGN-binding capacity were more prone to blocking by DC-SIGN mAb in MLR than PBL from a donor with low DC-SIGN-binding capacity. This study indicates an initial and transient role for DC-SIGN in T cell proliferation, which becomes apparent when T cell proliferation is low and when the percentage of DC-SIGN binding PBL is high.
authors.affiliation: Department of Tumor Immunology, NCMLS 278, Radboud University Nijmegen Medical Centre, Geert Grooteplein 26/28, 6525 GA Nijmegen, The Netherlands.
authors.forename: Karlijn
authors.initials: K
authors.lastname: Gijzen
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Tacken
authors.forename: Aukje
authors.initials: A
authors.lastname: Zimmerman
authors.forename: Ben
authors.initials: B
authors.lastname: Joosten
authors.forename: I Jolanda M
authors.initials: IJ
authors.lastname: de Vries
authors.forename: Carl G
authors.initials: CG
authors.lastname: Figdor
authors.forename: Ruurd
authors.initials: R
authors.lastname: Torensma
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D007959:Lymphocyte Culture Test, Mixed; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D016169:Lymphocyte Function-Associated Antigen-1; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C062279:CD6 antigen