Antithymocyte globulin impairs T-cell/antigen-presenting cell interaction: disruption of immunological synapse and conjugate formation.
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.
Haidinger
Michael
M
Clinical Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Geyeregger
René
R
Poglitsch
Marko
M
Weichhart
Thomas
T
Zeyda
Maximilian
M
Vodenik
Barbara
B
Stulnig
Thomas M
TM
Böhmig
Georg A
GA
Hörl
Walter H
WH
Säemann
Marcus D
MD
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
D000961:Antilymphocyte Serum; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D007166:Immunosuppressive Agents; D011948:Receptors, Antigen, T-Cell