The effect of cyclosporin-A, low-temperature culture, and anti-Ia antibodies on prevention of rejection of rat islet allografts.
The effect of cyclosporin-A, low-temperature culture, and anti-Ia antibodies on prevention of rejection of rat islet allografts was determined. Wistar-Furth islets were isolated by the collagenase technique and transplanted via the portal vein into diabetic Lewis recipients. Cyclosporin-A (30 mg/kg) injected at 0, 1, and 2 days after transplantation produced a significant prolongation of survival of the islet allografts (MST greater than 35.7 +/- 7.0 days) when hand-picked donor islets were used, whereas only a modest prolongation of survival (14.0 +/- 1.6 days) was obtained using donor islets removed directly from Ficoll gradients. This difference in survival was apparently due to the large number of lymphoid, antigen-presenting cells that were present in the islet fraction removed directly from the Ficoll gradients. Treatment of donor, hand-picked islets with a mixture of cross-reactive anti-Ia antibodies and complement without cyclosporin-A therapy did not prolong the survival of islet allografts (MST, 6.5 +/- 0.4 days versus 7.0 +/- 0.5 days in controls). In contrast, treatment of the donor islets with the mixture of anti-Ia antibodies and complement in conjunction with the 3-day course of cyclosporin-A therapy produced an 83% survival of the islet allografts at 60 days after transplantation. In vitro culture of hand-picked donor islets at 24 degrees C for 7 days and the 3-day course of cyclosporin-A therapy produced a 100% survival of the allografts at 60 days after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
Terasaka
R
R
Lacy
P E
PE
Hauptfeld
V
V
Bucy
R P
RP
Davie
J M
JM
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001786:Blood Glucose / Q000032:analysis; D003080:Cold Temperature; D003524:Cyclosporins / Q000494:pharmacology*; D006084:Graft Rejection / Q000187:drug effects*; D006085:Graft Survival / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014184:Transplantation, Homologous
D000906:Antibodies; D001786:Blood Glucose; D003524:Cyclosporins; D000949:Histocompatibility Antigens Class II