Activation of natural killer T cells enhances the function of regulatory T-cell therapy in suppressing murine GVHD

  • Toshihito Hirai
    Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University, Stanford, CA;
  • Po-Yu Lin
    Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University, Stanford, CA;
  • Federico Simonetta
    Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University, Stanford, CA;
  • Kristina Maas-Bauer
    Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University, Stanford, CA;
  • Mustafa Turkoz
    Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University, Stanford, CA;
  • Melissa Mavers
    Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University Medical Center, Stanford, CA; and
  • Jeanette Baker
    Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University, Stanford, CA;
  • Robert S. Negrin
    Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University, Stanford, CA;

抄録

<jats:p>Cellular therapy with regulatory T cells (Tregs) has shown promising results for suppressing graft-versus-host disease (GVHD) while preserving graft vs tumor effects in animal models and phase 1/2 clinical trials. However, a paucity of Tregs in the peripheral blood makes it difficult to acquire sufficient numbers of cells and hampers further clinical application. Invariant natural killer T (iNKT) cells constitute another compartment of regulatory cells that ameliorate GVHD through activation of Tregs after their own activation with α-galactosylceramide (α-GalCer) or adoptive transfer. We demonstrate here that a single administration of α-GalCer liposome (α-GalCer-lipo) enhanced the in vivo expansion of Tregs after adoptive transfer in a murine GVHD model and improved therapeutic efficacy of Treg therapy even after injection of otherwise suboptimal cell numbers. Host iNKT cells rather than donor iNKT cells were required for GVHD suppression because the survival benefit of α-GalCer-lipo administration was not shown in the transplantation of cells from wild-type (WT) C57BL/6 mice into Jα18−/− iNKT cell–deficient BALB/c mice, whereas it was observed from Jα18−/− C57BL/6 donor mice into WT BALB/c recipient mice. The combination of iNKT cell activation and Treg adoptive therapy may make Treg therapy more feasible and safer by enhancing the efficacy and reducing the number of Tregs required.</jats:p>

収録刊行物

  • Blood Advances

    Blood Advances 5 (11), 2528-2538, 2021-06-08

    American Society of Hematology

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