Costimulatory blockade with mTor inhibition abrogates effector T‐cell responses allowing regulatory T‐cell survival in renal transplantation |
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Authors: | Oriol Bestard Linda Cassis Josep M Cruzado Joan Torras Marcella Franquesa Salvador Gil‐Vernet Marc Lucia Josep M Grinyó |
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Institution: | 1. Nephrology Department, Renal Transplant Unit, Bellvitge University Hospital, University of Barcelona, Barcelona, Spain;2. Experimental Nephrology Department, IDIBELL, University of Barcelona, Barcelona, Spain;3. Experimental Nephrology Department, IDIBELL, University of Barcelona, Barcelona, Spain |
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Abstract: | The advent of novel immunosuppressive strategies in renal transplantation, with immunomodulatory properties, might facilitate long‐term allograft survival. T‐cell depletion, costimulation‐blockade and mTor inhibition have been shown to favour anti‐donor hyporesponsiveness. Recently, the combination of rATG, belatacept (Bela) and sirolimus (SRL) has been used in kidney transplantation, showing very low incidence of acute rejection and excellent 12‐month graft and patient survival. Herein, we have analysed the 1‐year evolution of memory/effector and regulatory T cells and assessed the donor‐specific T‐cell alloimmune response in a group of these patients and compared with others treated with a calcineurin‐inhibitor(CNI)‐based (rATG/tacrolimus/MMF), and two other Bela‐based regimens (rATG/Bela/MMF and basiliximab/Bela/MMF/steroids). During the first year after transplantation, patients receiving rATG/Bela/SRL had significantly higher percentage of Tregs upon the memory T‐cell compartment and showed a potent anti‐donor suppressive activity. In an in vitro naive and memory/effector T‐cell co‐culture, the combination of costimulation‐blockade and SRL could abrogate both antigen‐specific T‐cell responses as efficiently as using a CNI drug. The combination of T‐cell depletion, costimulation‐blockade and mTor inhibition seems to be able to allow Treg survival and inhibit donor‐specific alloreactive effector immune responses after kidney transplantation in humans. |
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Keywords: | costimulation‐blockade mTor‐inhibition regulatory T cells renal transplantation T‐cell depletion tolerance |
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