Cell surface modification by activated polyethylene glycol prevents allosensitization after islet transplantation.
The necessity to transplant islet tissue without the need for immunosuppressant therapy has led to the development of materials for immune modulation. Pegylation makes islets antigenically silent, protecting them from the adsorption of foreign protein and thus avoiding immune injury. The aim of this study is to determine whether pegylation of islets prolongs islet survival and function both during tissue culture and posttransplantation. We used cyanuric chloride-activated methoxy-polyethylene glycol for cell surface modification. To detect the pegylation effect on splenocytes, we measured antibody binding inhibition and abrogation of lymphocyte proliferation. To detect the pegylation effect on islet grafts, we performed rodent islet transplantation. Islet viability and function were maintained after pegylation. Pegylated islets showed a 90% decrease in antibody binding and decreased lymphocyte proliferation in a mixed lymphocyte culture. However, when pegylated islets were transplanted, no prolongation of graft survival was observed. When a subtherapeutic dose of immunosuppressant was given at the time of transplantation of pegylated islets, islet graft survival was significantly prolonged. In addition, when rats were sensitized with donor splenocytes, graft survival was prolonged by pegylation. We observed that pegylation of islets, combined with a subtherapeutic dose of immunosuppressant, protects the graft from rejection. Prolonged graft survival in sensitized recipients showed that pegylation of islets shifted the pattern of rejection from an acute humoral response to a less aggressive cellular alloresponse.
Wee
Yu-Mee
YM
Department of Surgery, Ulsan University College of Medicine & Asan Medical Center, Seoul, 138-736, Korea.
Lim
Dong-Gyun
DG
Kim
Yang-Hee
YH
Kim
Jin-Hee
JH
Kim
Song-Cheol
SC
Yu
EunSil
E
Park
Myung-Ok
MO
Choi
Monica Young
MY
Park
Youn-Hee
YH
Jang
Hyuk-Jai
HJ
Cho
Eun-Young
EY
Cho
Myung-Hwan
MH
Han
Duck-Jong
DJ
D000818:Animals; D000954:Antigens, Surface / Q000187:drug effects* / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000628:therapy*; D006084:Graft Rejection / Q000517:prevention & control*; D007165:Immunosuppression Therapy / Q000379:methods; D007515:Islets of Langerhans / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D016381:Islets of Langerhans Transplantation / Q000276:immunology / Q000379:methods*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D013311:Streptozocin; D013499:Surface Properties / Q000187:drug effects; D023001:Transplantation Tolerance / Q000187:drug effects; D014227:Triazines / Q000494:pharmacology
D000954:Antigens, Surface; D003432:Cross-Linking Reagents; D014227:Triazines; D011092:Polyethylene Glycols; C019309:cyanuric chloride; D013311:Streptozocin