Regulatory dendritic cell therapy in organ transplantation

Authors

  • Kenneth R. McCurry,

    1.  Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
    2.  Departments of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
    3.  Heart, Lung and Esophageal Surgery Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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  • Bridget L. Colvin,

    1.  Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
    2.  Departments of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
    3.  Department of Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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  • Alan F. Zahorchak,

    1.  Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
    2.  Departments of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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  • Angus W. Thomson

    1.  Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
    2.  Departments of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
    3.  Department of Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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Kenneth R. McCurry MD, FACS, Thomas E. Starzl Transplantation Institute and Heart, Lung and Esophageal Surgery Institute, University of Pittsburgh Medical Center, 200 Lothrop Street, Suite C-700, Pittsburgh, PA 15213, USA. Tel.: +1 412 648 6352; fax: +1 412 648 6354; e-mail: mccurrykr@upmc.edu and
Bridget L. Colvin PhD, Thomas E. Starzl Transplantation Institute and Depts of Surgery and Immunology, University of Pittsburgh Medical Center, E1504 BST 200 Lothrop St., Pittsburgh, PA15213, USA. Tel.: +1 412 624 6502; fax: +1 412 624 1172; e-mail: colibl@upmc.edu

Summary

Dendritic cells (DCs) are uniquely well equipped antigen (Ag)-presenting cells. Their classic function was thought to be that of potent initiators of innate and adaptive immunity to infectious organisms and other Ags (including transplanted organs). Evidence has emerged, however, that DCs have a central and crucial role in determining the fate of immune responses toward either immunity or tolerance. This dichotomous function of DCs, coupled with their remarkable plasticity, renders them attractive therapeutic targets for immune modulation. In transplantation, much recent work has focused on the ability of DCs to silence immune reactivity in an Ag-specific manner in the hope of preventing rejection and diminishing reliance on potentially harmful immunosuppressive agents. Experimental strategies have included in vivo targeting of DCs, as well as ex vivo generation of regulatory (or tolerogenic) DCs with subsequent reinfusion (i.e. cell therapy). Different approaches to ‘program’ DC toward tolerogenic properties include genetic (transgene insertion), biologic (differential culture conditions, anti-inflammatory cytokine exposure) and pharmacologic manipulation. Recent data suggest a promising role for pharmacologic treatment as a means of generating potent regulatory DCs and have further stimulated speculation regarding their potential clinical application. Herein, we discuss evidence that the potential of regulatory DC therapy is considerable and that there are compelling reasons to evaluate it in the setting of organ transplantation in the near future.

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