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.
McKenna
Gregory J
GJ
Department of Surgery, University of British Columbia, 3100-910 West 10th Avenue, Vancouver, BC, Canada, V5Z 4E3.
Kim
Peter T W
PT
Mui
Alice L F
AL
Ong
Christopher J
CJ
Rotstein
Ori D
OD
Warnock
Garth L
GL
Chung
Stephen W
SW
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D005978:Glutathione / Q000494:pharmacology*; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000166:cytology; D012313:RNA / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000637:transplantation; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D018799:Intercellular Adhesion Molecule-1; D012313:RNA; D005978:Glutathione