Donor-specific antigen and cyclosporine in rat islet allografts.
Combination therapy with one dose of 3 M KCl extracted donor-soluble antigen (Ag) and a short course of cyclosporine (CsA) has proven to prolong the survival of kidney allografts by enhancing specific T-suppressor populations. This regimen is tested in rat islet allografts in this study (Lewis to ACI). A 3-day perioperative course of 10 mg/kg/day CsA on Days -1, 0, and 1 did not prolong graft survival (MST = 10.7 +/- 2.5 days vs 9.4 +/- 1.2 days in controls). When this course of CsA therapy was combined with a single dose of donor antigen on Day -1, the survival time was prolonged slightly but significantly (MST = 14.0 +/- 5.8 days). Three cycles of a 3-day course of CsA therapy at 7-day intervals, a total of nine doses of 10 mg/kg/day CsA, were effective in delaying rejection of islet allografts (MST = 26.4 +/- 30.3). Moreover, combined therapy with donor antigen and three cycles of a 3-day course of CsA prolonged the survival of islet allografts (MST = 57.7 +/- 51.4 days) with 50% of recipients still normoglycemic at 60 days after transplantation. These findings indicate that the combination therapy of donor antigen with a short course of CsA has a powerful effect to prevent the rejection of islet allografts, as shown in kidney allografts, in rats.
D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D003524:Cyclosporins / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000601:surgery; D006082:Graft Enhancement, Immunologic / Q000379:methods*; D006084:Graft Rejection / Q000187:drug effects*; D007515:Islets of Langerhans / Q000276:immunology; D016381:Islets of Langerhans Transplantation; D008297:Male; D051381:Rats; D011912:Rats, Inbred ACI; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew / Q000276:immunology; D016038:Skin Transplantation
D000941:Antigens; D003524:Cyclosporins