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

Background Pretransplant 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. Methods Splenic 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. Results GSH 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. Conclusions GSH depletion may represent a significant immunomodulator of donor antigenicity to prevent transplant rejection.