Glutathione depletion of stimulator cells inhibits responder T-cell immunogenicity in vitro and prolongs allograft survival in vivo

BackgroundPretransplant donor-organ immunomodulation may attenuate allograft rejection by changing the redox state of donor cells. This study explored impact of donor-cell redox-state alteration by glutathione (GSH) depletion on graft immunogenicity.MethodsSplenic and heart endothelial cells from Balb/c mice were treated with diethylmaleate (a GSH-depleting agent) and/or lipopolysaccharide to assess the impact of GSH depletion on alloreactivity by mixed lymphocyte reaction, endothelial cell adhesion by T-cell adhesion assay, intracellular adhesion molecule-1 expression by reverse transcriptionase–polymerase chain reaction, and nuclear factor–kappa B upregulation by electrophoretic mobility shift assay. Heterotopic heart transplants were performed as in vivo correlate.ResultsGSH depletion decreased endothelial cell and splenic cell alloreactivity, decreased endothelial cell intracellular adhesion molecule-1 expression through attenuation of nuclear factor–kappa B activity, decreased endothelial cell adhesion, and prolonged heterotopic heart transplant graft survival.ConclusionsGSH depletion may represent a significant immunomodulator of donor antigenicity to prevent transplant rejection.