Does intrathymic injection of alloantigen-presenting cells before islet allo-transplantation prolong graft survival?
Current immunosuppressive agents have potentially dangerous side-effects, are non-specific and most are also diabetogenic. We investigated tolerance induction with intrathymic injection of purified antigen-presenting cells (APC) plus a single dose of antilymphocyte serum (ALS) intraperitoneally before allogeneic islet transplantation in the rat model WAG to Lewis (RT1u to RT1l). Purified donor APC [non-parenchymal cells (NPC) or dendritic cells (DC)] were prepared from liver and spleen, respectively. Isograft function for more than 120 days proved that islet isolation, purification and transplantation procedures were adequate. A total of WAG DC (4 x 10(5)) or NPC (2 x 10(6)) in 20 microl were injected into both lobes of the thymus of 140-210 g Lewis recipients followed by a single injection of ALS. Three days later, diabetes was induced with streptozotocin (60 mg/kg). Four days later allogeneic islets were grafted into the liver by intraportal injection of 3000 WAG islets. Control animals (n = 8) received 20 microl saline intrathymically instead of APC. Graft function was assessed by blood glucose measurements with glucose levels above 15 mmol/l on 3 consecutive days defined as graft rejection. Animals given DC (n = 9) or NPC (n = 8) intrathymically plus 1 ml of ALS, rejected their grafts in an accelerated fashion with a median survival time (MST) of 3 days. However, control animals rejected their grafts with a MST of 7 days, but with two animals surviving for more than 2 months. In conclusion, intrathymic inoculation with purified APC plus a single dose of ALS did not prolong allogeneic islet graft function but induced accelerated rejection of the islet allografts.
Chaib
E
E
Department of Surgery, University of Cambridge, Addenbrookes Hospital, UK.
Brons
I G
IG
Papalois
A
A
Calne
R Y
RY
D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology*; D000961:Antilymphocyte Serum / Q000494:pharmacology; D017690:Cell Transplantation; D003713:Dendritic Cells / Q000166:cytology*; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D006085:Graft Survival / Q000276:immunology*; D007165:Immunosuppression Therapy / Q000379:methods; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013950:Thymus Gland; D014184:Transplantation, Homologous / Q000276:immunology*
D000961:Antilymphocyte Serum