title: Characteristics of antigen-independent and antigen-dependent interaction of dendritic cells with CD4+ T cells.
abstract: Dendritic cells (DC) are the main antigen-presenting cells for the initiation of primary T cell-mediated immune responses. In the first stage of activation, T cells bind to DC in an antigen-independent manner. We studied the adhesion characteristics of human CD4+ T cells to DC generated from CD34+ hematopoietic progenitors following 12 to 13 days of culture in the presence of granulocyte/macrophage colony-stimulating factor and tumor necrosis factor-alpha. A majority of these cells had the morphology, phenotype and functions of DC. CD4+ T/DC adhesion was measured by means of fluorescence microscopy and flow cytometry. Four independent receptor/ligand pathways, LFA-1/ICAM, ICAM/LFA-1, CD2/LFA-3 and CD28/CD80, were involved in the transient adhesion of DC to CD4+ T cells in antigen-independent and specific alloantigen-dependent situations, as shown by blocking experiments using monoclonal antibodies. The antibodies also blocked a primary mixed lymphocyte reaction (MLR) in which DC were used as stimulatory cells. Adhesion of alloreactive CD4+ T cells to antigen-presenting DC was stronger than that of resting CD4+ T cells, while peak adhesion occurred after 5 and 20 min, respectively. The LFA-1 ligands involved in adhesion of resting CD4 T cells to DC and alloreactive CD4+ T cells to specific DC differed in part, since ICAM-3 on resting T cells and ICAM-1 on alloreactive T lymphocytes preferentially bound LFA-1. Studies of interactions between DC and phorbol ester-activated T cells expressing the CD40 ligand revealed a fifth independent adhesion pathway, CD40/CD40 ligand. CD4-mediated regulation of CD4+ T/DC adhesion was suggested by the observation that preincubation of CD4+ T cells and DC individually with anti-CD4 antibodies inhibited adhesion. In addition, antibodies specific for HLA class II molecules inhibited adhesion when used to pretreat DC but not alloactivated CD4+ T cells.
authors.affiliation: INSERM U429, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Hauss
authors.forename: F
authors.initials: F
authors.lastname: Selz
authors.forename: M
authors.initials: M
authors.lastname: Cavazzana-Calvo
authors.forename: A
authors.initials: A
authors.lastname: Fischer
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology; D018949:Antigens, CD1; D018952:Antigens, CD34; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D001854:Bone Marrow Cells; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D019013:CD40 Antigens; D023201:CD40 Ligand; D002448:Cell Adhesion / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000502:physiology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism*; D005312:Fetal Blood / Q000166:cytology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D006681:HLA-D Antigens / Q000276:immunology; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018949:Antigens, CD1; D018952:Antigens, CD34; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D015815:Cell Adhesion Molecules; D006681:HLA-D Antigens; D007519:Isoantigens; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D015759:Ionomycin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013755:Tetradecanoylphorbol Acetate