title: Antithymocyte globulin impairs T-cell/antigen-presenting cell interaction: disruption of immunological synapse and conjugate formation.
abstract: Antithymocyte globulin (ATG) is employed for the treatment and prevention of acute organ rejection after transplantation. However, the mechanisms underlying its immunomodulatory capacities beyond cellular depletion remains ill defined. A stable interaction between T-cells and professional antigen-presenting cells (APC) and full T-cell stimulation requires a complex molecular rearrangement at the T-cell/APC interface, the so called immunological synapse. Here we investigated, whether ATG affects T-cell/APC interactions. ATG concentration and time-dependently inhibited relocalization of the T-cell receptor/CD3 complex as well as adhesion molecules and cytoskeletal proteins of human peripheral blood T-cells and a human T-cell line towards the APC contact site. Moreover, ATG-treated peripheral blood T-cells were incapable to form conjugates with APCs. In conclusion, ATG impairs T-cell/APC conjugate formation, a mechanism that may help to understand the functional inactivation of peripheral blood T-cells that have escaped cellular depletion after ATG treatment.
authors.affiliation: Clinical Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Haidinger
authors.forename: René
authors.initials: R
authors.lastname: Geyeregger
authors.forename: Marko
authors.initials: M
authors.lastname: Poglitsch
authors.forename: Thomas
authors.initials: T
authors.lastname: Weichhart
authors.forename: Maximilian
authors.initials: M
authors.lastname: Zeyda
authors.forename: Barbara
authors.initials: B
authors.lastname: Vodenik
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Stulnig
authors.forename: Georg A
authors.initials: GA
authors.lastname: Böhmig
authors.forename: Walter H
authors.initials: WH
authors.lastname: Hörl
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Säemann
mesh_terms: D000938:Antigen-Presenting Cells / Q000502:physiology*; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000494:pharmacology*; D017252:CD3 Complex / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects*; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019169:Jurkat Cells; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology*; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D000961:Antilymphocyte Serum; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D007166:Immunosuppressive Agents; D011948:Receptors, Antigen, T-Cell