title: Regulatory T cells form stable and long-lasting cell cluster with myeloid dendritic cells (DC).
abstract: Regulatory T cells (Treg) with the capacity to suppress T-cell proliferation exert various effects on T cell function. In addition, Treg have been shown to modulate the phenotype and function of antigen-presenting cells (APC) including dendritic cells (DC), B cells and monocytes/macrophages. However, the specific mechanism(s) of how Treg affect APC have not been entirely identified so far. In this study, we analyzed the interaction of human Treg and effector T cells (Teff) with peripheral blood myeloid and monocyte-derived dendritic cells in vitro. A strong tendency for cell cluster formation between Treg and DC was observed, which was dependent on the adhesion molecules ICAM-1, LFA-3 and ICAM-3. In addition, Treg were found to express higher levels of LFA-1, LFA-2, LFA-3 and ICAM-3 both before and after activation with anti-CD3 antibodies. Using in vitro live cell imaging, we were further able to show that Treg-DC cell clusters, in contrast to Teff-DC clusters, were stable and long lasting. Co-cultures of DC with Treg diminished the up-regulation of activation induced costimulatory molecule expression on DC, and further reduced the production of tumor necrosis factor alpha and stimulated the production of IL-4. In summary, our data indicate that Treg-DC cluster formation might enable Treg to modulate phenotypic and functional characteristics of DC and help to constrain Teff activation.
authors.affiliation: Division of Rheumatology, Center of Physiology, Pathophysiology and Immunology, Medical University of Vienna, Austria.
authors.forename: Sonja
authors.initials: S
authors.lastname: Herman
authors.forename: Dagmar
authors.initials: D
authors.lastname: Krenbek
authors.forename: Michael
authors.initials: M
authors.lastname: Klimas
authors.forename: Michael
authors.initials: M
authors.lastname: Bonelli
authors.forename: Carl W
authors.initials: CW
authors.lastname: Steiner
authors.forename: Peter
authors.initials: P
authors.lastname: Pietschmann
authors.forename: Josef S
authors.initials: JS
authors.lastname: Smolen
authors.forename: Clemens
authors.initials: C
authors.lastname: Scheinecker
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000276:immunology; D022423:Myeloid Cells / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4