Regulatory T cell therapy: An option to induce operational tolerance in liver transplantation.
Regulatory T cells (Treg) may play an important role in operational (clinical) tolerance (OT), a stable graft function without immunosuppression in an otherwise immunocompetent host, that is spontaneously observed in some patients many years after transplantation. Several ongoing clinical trials are currently testing the effects of donor-specific or non-specific Treg infusion with the goal to induce this state of OT a few months after liver transplantation (LT). The preliminary results of two of these trials have been recently published, and raise a number of comments and issues: (1) These two papers demonstrate that a 100 to 1000-fold ex-vivo expansion of Treg is possible in humans after 2 weeks of culture. The optimal human Treg dose is however not clearly established, and might be higher than the dose that would be expected from translating murine data. (2) A lot of concerns are remaining regarding the Treg purity before expansion, the Treg stability during in vitro culture and the in vivo fate of infused cells. A strict monitoring of Treg should thus be done at each step. (3) Since Treg may play a detrimental role in some conditions, such as viral diseases and cancer, potential LT recipients with such diseases should probably be excluded from the initial trials of Treg infusion. (4) The follow-up of tolerant liver recipients should include repeated liver biopsies and detection of autoantibodies and humoral response, in addition to conventional liver graft assessment, in order to prevent the development of immune complications related to immunosuppression withdrawal. (5) The final issue raised by Treg therapy in LT is the choice of the immunosuppressive regimen used before tapering or withdrawal, appropriate to preserve OT establishment.
AP-HP, Hôpital de la Pitié-Salpêtrière, 75013 Paris, France; France Sorbonne universités, UPMC université Paris 06, 75006 Paris, France.
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Conti
Cliniques universitaires Saint-Luc, 1200 Bruxelles, Belgium. Electronic address: geraldine.dahlqvist@uclouvain.be.
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Dahlqvist
AP-HP, Hôpital de la Pitié-Salpêtrière, 75013 Paris, France. Electronic address: helbrisson@hotmail.com.
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Brisson
AP-HP, Hôpital de la Pitié-Salpêtrière, 75013 Paris, France; France Sorbonne universités, UPMC université Paris 06, 75006 Paris, France. Electronic address: makoto.miyara@gmail.com.
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Miyara
AP-HP, Hôpital de la Pitié-Salpêtrière, 75013 Paris, France; France Sorbonne universités, UPMC université Paris 06, 75006 Paris, France. Electronic address: guy.gorochov@upmc.fr.
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Calmus
AP-HP, Hôpital de la Pitié-Salpêtrière, 75013 Paris, France; France Sorbonne universités, UPMC université Paris 06, 75006 Paris, France.
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Gorochov
D002478:Cells, Cultured; D002986:Clinical Trials as Topic; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007167:Immunotherapy / Q000379:methods*; D016031:Liver Transplantation; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*
D007166:Immunosuppressive Agents