title: Antithymocyte Globulin Induces a Tolerogenic Phenotype in Human Dendritic Cells.
abstract: Antithymocyte globulin (ATG) is used in the prevention of graft-versus-host disease during allogeneic hematopoietic stem cell transplantation. It is generally accepted that ATG mediates its immunosuppressive effect primarily via depletion of T cells. Here, we analyzed the impact of ATG-Fresenius (now Grafalon®) on human monocyte-derived dendritic cells (DC). ATG induced a semi-mature phenotype in DC with significantly reduced expression of CD14, increased expression of HLA-DR, and intermediate expression of CD54, CD80, CD83, and CD86. ATG-DC showed an increase in IL-10 secretion but no IL-12 production. In line with this tolerogenic phenotype, ATG caused a significant induction of indoleamine 2,3-dioxygenase expression and a concomitant increase in levels of tryptophan metabolites in the supernatants of DC. Further, ATG-DC did not induce the proliferation of allogeneic T cells in a mixed lymphocyte reaction but actively suppressed the T cell proliferation induced by mature DC. These data suggest that besides its well-known effect on T cells, ATG modulates the phenotype of DC in a tolerogenic way, which might constitute an essential part of its immunosuppressive action in vivo.
authors.affiliation: Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany. roidertobias@gmail.com.
authors.forename: Tobias
authors.initials: T
authors.lastname: Roider
authors.affiliation: Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany. michael.katzfuss@puk.zh.ch.
authors.forename: Michael
authors.initials: M
authors.lastname: Katzfuß
authors.affiliation: Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany. carina.matos@ukr.de.
authors.forename: Carina
authors.initials: C
authors.lastname: Matos
authors.affiliation: Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany. katrin.singer@ukr.de.
authors.forename: Katrin
authors.initials: K
authors.lastname: Singer
authors.affiliation: Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany. kathrin.renner-sattler@ukr.de.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Renner
authors.affiliation: Institute of Functional Genomics, University of Regensburg, Am BioPark 9, 93053 Regensburg, Germany. peter.oefner@ukr.de.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Oefner
authors.affiliation: Institute of Functional Genomics, University of Regensburg, Am BioPark 9, 93053 Regensburg, Germany. katja.dettmer@ukr.de.
authors.forename: Katja
authors.initials: K
authors.lastname: Dettmer-Wilde
authors.affiliation: Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany. wolfgang.herr@ukr.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Herr
authors.affiliation: Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany. ernst.holler@ukr.de.
authors.forename: Ernst
authors.initials: E
authors.lastname: Holler
authors.affiliation: Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany. marina.kreutz@ukr.de.
authors.forename: Marina
authors.initials: M
authors.lastname: Kreutz
authors.affiliation: Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany. katrin.peter@ukr.de.
authors.forename: Katrin
authors.initials: K
authors.lastname: Peter
mesh_terms: D000961:Antilymphocyte Serum / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014364:Tryptophan / Q000378:metabolism
chemical_list: D000961:Antilymphocyte Serum; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012333:RNA, Messenger; D016753:Interleukin-10; D014364:Tryptophan
keywords: Grafalon; allogeneic hematopoietic stem cell transplantation; antithymocyte globulin; dendritic cell; immunosuppressive; indoleamine 2,3-dioxygenase; tolerogenic