Antithymocyte Globulin Induces a Tolerogenic Phenotype in Human Dendritic Cells

Roider, Tobias and Katzfuss, Michael and Matos, Carina and Singer, Katrin and Renner, Kathrin and Oefner, Peter J. and Dettmer-Wilde, Katja and Herr, Wolfgang and Holler, Ernst and Kreutz, Marina and Peter, Katrin (2016) Antithymocyte Globulin Induces a Tolerogenic Phenotype in Human Dendritic Cells. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 17 (12): 2081. ISSN 1422-0067,

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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 (R)) 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.

Item Type: Article
Uncontrolled Keywords: REGULATORY T-CELLS; ARYL-HYDROCARBON RECEPTOR; INDOLEAMINE 2,3-DIOXYGENASE; TRYPTOPHAN CATABOLISM; IN-VITRO; EXPRESSION; TRANSPLANTATION; ACTIVATION; MECHANISMS; MONOCYTES; allogeneic hematopoietic stem cell transplantation; dendritic cell; antithymocyte globulin; Grafalon; tolerogenic; indoleamine 2,3-dioxygenase; immunosuppressive
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner)
Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 12 Apr 2019 06:11
Last Modified: 12 Apr 2019 06:11
URI: https://pred.uni-regensburg.de/id/eprint/3833

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