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Updated: Aug 23, 2026
Induction of Graft-versus-host Disease and In Vivo T Cell Monitoring Using an MHC-matched Murine Model
Published on: August 29, 2012
Effect of KRN7000 on induced graft-vs-host disease
Shoshana Morecki1, Soumya Panigrahi, Galina Pizov
1Department of Bone Marrow Transplantation & Cancer Immunotherapy, Cell Therapy & Transplantation Research Center, Hadassah University Hospital, Jerusalem, Israel. morecki@hadassah.org.il
Objective:
Graft-vs-host disease (GVHD) is a serious complication of allogeneic stem cell transplantation (SCT) and donor lymphocyte infusion (DLI), for which no effective therapy exists. In our study, KRN7000, a synthetic analog of alpha-galactosylceramide, known for its ability to activate natural killer T cells, was tested for its ability to prevent onset of GVHD in a murine model of haploidentical major histocompatible (MHC) mismatched hematopoietic cells.
Methods:
Irradiated (BALB/cXC57BL/6)F1 mice were inoculated with parental C57BL/6 splenocytes with or without SCT. KRN7000 was given intraperitoneally as single or multiple doses at 100 microg/kg/dose and mice were followed up for GVHD clinical symptoms and for survival. The effect of KRN7000 treatment was also tested in vitro for the induction of suppression of alloreactivity in mixed lymphocyte reaction (MLR).
Results:
KRN7000 prevented development of GVHD symptoms in almost all mice and 52/53 mice maintained a healthy profile for more than 235 days. Most vehicle-treated mice or untreated controls died of GVHD within a median of 3 weeks. KRN7000 treatment did not prevent engraftment of donor cells following sublethal total-body irradiation (TBI) and allowed durable persistence of donor cells following lethal TBI and SCT. Splenocytes derived from KRN7000-treated mice suppressed efficiently mixed lymphocyte reaction (MLR) in vitro.
Conclusion:
GVHD induced by alloreactive lymphocytes can be prevented by KRN7000. GVHD prevention may be accomplished by regulation of T cell function and might thus provide a new modality for safer SCT and DLI.
