title: Novel molecular mechanisms of dendritic cell-induced T cell activation.
abstract: In this study we have re-examined the molecular mechanisms involved in activation of T cells by dendritic cells (DC). Human peripheral blood DC (PBDC) were derived by 2 h adhesion followed by 7 day culture in a combination of granulocyte macrophage colony stimulating factor and IL-4, and depletion of residual T and B cells. These PBDC were used to induce autologous T cell proliferation in a CD3-dependent response, and antibodies against CD11a/18 and CD86 were used as control inhibitors of accessory function. Antibodies against five of the cell surface molecules that we have recently identified on the surface of DC, CD13, CD87, CD98, CD147 and CD148, and an antibody which recognizes a molecule that has not as yet been identified, all inhibited the CD3-induced T cell proliferation. These findings were observed not only when antibodies were present throughout the culture, but also when they were prepulsed on to the surface of the DC, suggesting the inhibition was mediated via the antigen-presenting cells rather than the T cell. The same set of antibodies also inhibited an allospecific mixed lymphocyte reaction, confirming that the inhibitory effect was not dependent on the use of a CD3 antibody as the stimulating agent. All the antibodies of known specificity inhibited both CD4 and CD8 T cells equally. Unlike CD87, CD98 and CD147 antibodies, which inhibited activation of both CD45RA (naive) T cells and CD45RO (memory) T cells, CD13 and CD148 appeared to be involved in activation of naive cells only. The molecules identified in this study have not previously been demonstrated to play a role as accessory molecules on DC, the cells that are pivotal for immune induction. Therefore they may provide new potential targets for modulation of the immune response at the APC level.
authors.affiliation: Department of Immunology, Windeyer Institute of Medical Sciences, UCL Medical School, 46 Cleveland Street, London W1P 6DB, UK.
authors.forename: V E
authors.initials: VE
authors.lastname: Woodhead
authors.forename: T J
authors.initials: TJ
authors.lastname: Stonehouse
authors.forename: M H
authors.initials: MH
authors.lastname: Binks
authors.forename: K
authors.initials: K
authors.lastname: Speidel
authors.forename: D A
authors.initials: DA
authors.lastname: Fox
authors.forename: A
authors.initials: A
authors.lastname: Gaya
authors.forename: D
authors.initials: D
authors.lastname: Hardie
authors.forename: A J
authors.initials: AJ
authors.lastname: Henniker
authors.forename: V
authors.initials: V
authors.lastname: Horejsi
authors.forename: K
authors.initials: K
authors.lastname: Sagawa
authors.forename: K M
authors.initials: KM
authors.lastname: Skubitz
authors.forename: H
authors.initials: H
authors.lastname: Taskov
authors.forename: R F
authors.initials: RF
authors.lastname: Todd
authors.forename: A
authors.initials: A
authors.lastname: van Agthoven
authors.forename: D R
authors.initials: DR
authors.lastname: Katz
authors.forename: B M
authors.initials: BM
authors.lastname: Chain
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000502:physiology; D018826:CD13 Antigens / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002352:Carrier Proteins / Q000502:physiology; D002450:Cell Communication; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology*; D027261:Fusion Regulatory Protein-1; D006801:Humans; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D017027:Protein Tyrosine Phosphatases / Q000502:physiology; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D011956:Receptors, Cell Surface / Q000502:physiology; D055293:Receptors, Urokinase Plasminogen Activator; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D002352:Carrier Proteins; D027261:Fusion Regulatory Protein-1; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D017493:Leukocyte Common Antigens; C486288:PTPRJ protein, human; D017027:Protein Tyrosine Phosphatases; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D018826:CD13 Antigens