Antithymocyte Globulin Induces a Tolerogenic Phenotype in Human Dendritic Cells

作者：Roider Tobias; Katzfuss Michael; Matos Carina; Singer Katrin; Renner Kathrin; Oefner Peter J; Dettmer Wilde Katja; Herr Wolfgang; Holler Ernst; Kreutz Marina; Peter Katrin^*

来源：International Journal of Molecular Sciences, 2016, 17(12): 2081.

DOI：10.3390/ijms17122081

• allogeneic hematopoietic stem cell transplantation
• dendritic cell
• antithymocyte globulin
• Grafalon
• tolerogenic
• indoleamine 2,3-dioxygenase
• immunosuppressive

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.

• 出版日期2016-12