title: Active MAC-1 (CD11b/CD18) on DCs inhibits full T-cell activation.
abstract: The beta2 integrins are important for transendothelial migration of leukocytes as well as for T-cell activation during antigen presentation. Despite abundant expression of beta2 integrins on antigen-presenting cells (APCs), their functional relevance for antigen presentation is completely unclear. We show here that dendritic cells (DCs) from CD18-deficient mice, which lack all functional beta2 integrins, have no defect in antigen presentation. Moreover, DCs from normal mice express inactive beta2 integrins that do not become activated on contact with T cells, at least in vitro. Pharmacologic activation of beta2 integrins on DCs results in a significant reduction of their T cell-activating capacity. This effect is mediated by Mac-1 (CD11b/CD18) on DCs because it could be reversed via blocking antibodies against CD18 and CD11b. Furthermore, the antigen-presenting capacity of macrophages, which express constitutively active beta2 integrins, is significantly enhanced on Mac-1 blockade. We therefore conclude that active CD11b/CD18 (Mac-1) on APCs directly inhibits T-cell activation.
authors.affiliation: Cell Biology, Department of Dermatology, University of Münster, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Varga
authors.forename: Sandra
authors.initials: S
authors.lastname: Balkow
authors.forename: Martin K
authors.initials: MK
authors.lastname: Wild
authors.forename: Andrea
authors.initials: A
authors.lastname: Stadtbaeumer
authors.forename: Mathias
authors.initials: M
authors.lastname: Krummen
authors.forename: Tobias
authors.initials: T
authors.lastname: Rothoeft
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Higuchi
authors.forename: Stefan
authors.initials: S
authors.lastname: Beissert
authors.forename: Klaus
authors.initials: K
authors.lastname: Wethmar
authors.forename: Karin
authors.initials: K
authors.lastname: Scharffetter-Kochanek
authors.forename: Dietmar
authors.initials: D
authors.lastname: Vestweber
authors.forename: Stephan
authors.initials: S
authors.lastname: Grabbe
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D039481:CD11b Antigen / Q000502:physiology*; D018821:CD18 Antigens / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000502:physiology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D039481:CD11b Antigen; D018821:CD18 Antigens; D016177:Macrophage-1 Antigen