The road to transplant tolerance is paved with good dendritic cells

Authors

  • Gilles Benichou,

    Corresponding author
    • Transplantation Research Center, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
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  • Georges Tocco

    1. Transplantation Research Center, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
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Full correspondence: Dr. Gilles Benichou, Massachusetts General Hospital, Department of Surgery, Thier 807, 55 Fruit Street, Boston, MA 02114, USA

Fax: +1-617-724-3901

e-mail: gbenichou@partners.org

See accompanying article by Khan et al.

Abstract

After transplantation, recipient T cells can recognize donor antigens either by interacting with MHC class II on donor bone marrow-derived cells (direct allorecognition), or by recognizing allogeneic peptides bound to self-MHC class II molecules on recipient antigen presenting cells (indirect allorecognition). The activation of pro-inflammatory T cells via either of these pathways leads to allograft rejection, so the suppression of both of these pathways is needed to achieve transplantation tolerance. A study in this issue of the European Journal of Immunology [Eur. J. Immunol. 2013. 43: 734–746] shows that allogeneic dendritic cells (DCs) modified to either lack expression of CD80/86 or over-express indoleamine 2,3-dioxygenase (IDO) are able to inhibit direct and/or indirect alloresponses in vitro and in vivo in mice. Notably, both allorecognition pathways were suppressed by the coexpression of self- and allo-MHC molecules on semi-allogeneic DCs. This Commentary discusses the challenges and potential of using genetically-modified DCs to suppress alloreactivity in the context of transplant tolerance.

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