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Updated: Jul 16, 2026

Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
Published on: May 18, 2018
Antithymocyte globulins suppress dendritic cell function by multiple mechanisms
Cord Naujokat1, Carsten Berges, Dominik Fuchs
1Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Heidelberg, Germany. cord.naujokat@med.uni-heidelberg.de
Background:
The polyclonal rabbit antithymocyte and anti-T-cell immunoglobulins (ATGs) Thymoglobulin (TG) and ATG-Fresenius S (ATG-F) have been widely used for the prevention and therapy of allograft rejection and graft versus host disease in transplantation. Although immunosuppressive mechanisms of ATGs on T cells are well studied, less is known about their impact on dendritic cells (DCs).
Methods:
Effects of TG and ATG-F on immune functions and signaling pathways of human monocyte-derived DCs were determined by flow cytometry, enzyme-linked immunosorbent assay, Western blot, apoptosis assays, endocytosis assays, and T cell stimulation assays.
Results:
TG and ATG-F bind rapidly and with high affinity to CD11c, CD80, CD86, CD40, CD36, CD38, CD206, and human leukocyte antigen-DR on DCs. TG and, to a lesser extent, ATG-F induce apoptosis in immature and mature DCs. Macropinocytotic and receptor-mediated endocytotic antigen uptake in immature DCs is inhibited by TG and ATG-F due to their binding of the C-type lectins CD206 and CD209. TG and ATG-F induce activation of the mitogen-activated protein kinases ERK1/2 and p38 that contributes to the induction of apoptosis. TG and ATG-F also induce cytoplasmic-nuclear translocation of the NF-kappaB/Rel transcription factors RelB, RelA, p50, and p52. Production of interleukin-12p70 in mature DCs is suppressed by TG and ATG-F. TG and ATG-F reduce the capacity of mature DCs to stimulate allogeneic and autologous T cells.
Conclusions:
ATGs interfere with basic DC functions, suggesting that DCs are relevant targets for the immunosuppressive action of ATGs in transplantation.
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