title: A role for interleukin-2 trans-presentation in dendritic cell-mediated T cell activation in humans, as revealed by daclizumab therapy.
abstract: Although previous studies have described CD25 expression and production of interleukin-2 (IL-2) by mature dendritic cells (mDCs), it remains unclear how these molecules participate in the activation of T cells. In search of the mechanisms by which daclizumab, a humanized monoclonal antibody against CD25, inhibits brain inflammation in multiple sclerosis, we observed that although the drug has limited effects on polyclonal T cell activation, it potently inhibits activation of antigen-specific T cells by mDCs. We show that mDCs (and antigen-experienced T cells) secrete IL-2 toward the mDC-T cell interface in an antigen-specific manner, and mDCs 'lend' their CD25 to primed T cells in trans to facilitate early high-affinity IL-2 signaling, which is crucial for subsequent T cell expansion and development of antigen-specific effectors. Our data reveal a previously unknown mechanism for the IL-2 receptor system in DC-mediated activation of T cells.
authors.affiliation: Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors.forename: Simone C
authors.initials: SC
authors.lastname: Wuest
authors.forename: Jehad H
authors.initials: JH
authors.lastname: Edwan
authors.forename: Jayne F
authors.initials: JF
authors.lastname: Martin
authors.forename: Sungpil
authors.initials: S
authors.lastname: Han
authors.forename: Justin S A
authors.initials: JS
authors.lastname: Perry
authors.forename: Casandra M
authors.initials: CM
authors.lastname: Cartagena
authors.forename: Eiji
authors.initials: E
authors.lastname: Matsuura
authors.forename: Dragan
authors.initials: D
authors.lastname: Maric
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Waldmann
authors.forename: Bibiana
authors.initials: B
authors.lastname: Bielekova
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D017951:Antigen Presentation / Q000187:drug effects; D000077561:Daclizumab; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000037:antagonists & inhibitors; D053646:Interleukin-2 Receptor beta Subunit / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D018448:Models, Immunological; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D023001:Transplantation Tolerance / Q000187:drug effects / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C508594:IL2 protein, human; C508017:IL2RA protein, human; C508020:IL2RB protein, human; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D053646:Interleukin-2 Receptor beta Subunit; D000077561:Daclizumab