Human monocyte-derived suppressor cells control graft-versus-host disease by inducing regulatory forkhead box protein 3-positive CD8+ T lymphocytes

Nona Janikashvili, Malika Trad, Alexandrine Gautheron, Maxime Samson, Baptiste Lamarthée, Francis Bonnefoy, Stéphanie Lemaire-Ewing, Marion Ciudad, Khatuna Rekhviashvili, Famky Seaphanh, Béatrice Gaugler, Sylvain Perruche, Andrew Bateman, Laurent Martin, Sylvain Audia, Philippe Saas, Nicolas Larmonier, Bernard Bonnotte

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Background Adoptive transfer of immunosuppressive cells has emerged as a promising strategy for the treatment of immune-mediated disorders. However, only a limited number of such cells can be isolated from in vivo specimens. Therefore efficient ex vivo differentiation and expansion procedures are critically needed to produce a clinically relevant amount of these suppressive cells. Objective We sought to develop a novel, clinically relevant, and feasible approach to generate ex vivo a subpopulation of human suppressor cells of monocytic origin, referred to as human monocyte-derived suppressive cells (HuMoSCs), which can be used as an efficient therapeutic tool to treat inflammatory disorders. Methods HuMoSCs were generated from human monocytes cultured for 7 days with GM-CSF and IL-6. The immune-regulatory properties of HuMoSCs were investigated in vitro and in vivo. The therapeutic efficacy of HuMoSCs was evaluated by using a graft-versus-host disease (GvHD) model of humanized mice (NOD/SCID/IL-2Rγc -/- [NSG] mice). Results CD33+ HuMoSCs are highly potent at inhibiting the proliferation and activation of autologous and allogeneic effector T lymphocytes in vitro and in vivo. The suppressive activity of these cells depends on signal transducer and activator of transcription 3 activation. Of therapeutic relevance, HuMoSCs induce long-lasting memory forkhead box protein 3-positive CD8+ regulatory T lymphocytes and significantly reduce GvHD induced with human PBMCs in NSG mice. Conclusion Ex vivo-generated HuMoSCs inhibit effector T lymphocytes, promote the expansion of immunosuppressive forkhead box protein 3-positive CD8+ regulatory T cells, and can be used as an efficient therapeutic tool to prevent GvHD.

Original languageEnglish (US)
Pages (from-to)1614-1624.e4
JournalJournal of Allergy and Clinical Immunology
Volume135
Issue number6
DOIs
StatePublished - Jun 1 2015

Keywords

  • Human monocyte-derived suppressor cells
  • T lymphocytes
  • graft-versus-host disease
  • inflammation
  • regulatory T cells
  • signal transducer and activator of transcription 3

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Janikashvili, N., Trad, M., Gautheron, A., Samson, M., Lamarthée, B., Bonnefoy, F., Lemaire-Ewing, S., Ciudad, M., Rekhviashvili, K., Seaphanh, F., Gaugler, B., Perruche, S., Bateman, A., Martin, L., Audia, S., Saas, P., Larmonier, N., & Bonnotte, B. (2015). Human monocyte-derived suppressor cells control graft-versus-host disease by inducing regulatory forkhead box protein 3-positive CD8+ T lymphocytes. Journal of Allergy and Clinical Immunology, 135(6), 1614-1624.e4. https://doi.org/10.1016/j.jaci.2014.12.1868