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. 2010 Mar 23;59(6):1469–1477. doi: 10.2337/db09-0502

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© 2010 by the American Diabetes Association.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

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FIG. 1. — EP1013 therapy, when combined with costimulation blockade using CTLA4-Ig, results in long-term islet graft survival and operational tolerance. A: Islet allografts were completed across a complete MHC mismatch using Balb/C (H-2d) donors and chemically diabetic B6 (H-2b) recipients. Caspase inhibitor therapy (EP1013) did not prolong graft survival compared with vehicle-treated animals. Monotherapy with CTLA4-Ig prevented graft rejection in 40% of recipients, whereas combination of EP1013 and CTLA4-Ig resulted in graft survival of >200 days in 89% of recipients (P < 0.01 vs. CTLA4-Ig). B: To test for donor-specific tolerance, graft-bearing kidneys were removed, and animals were re-transplanted with either donor-type (Balb/C) or third-party (C3H, H-2k) islets without further treatment or with a second 10-day course of EP1013. When using Balb/C islets, donor-specific tolerance was demonstrated in ∼30% of the transplant recipients (either CTL4-Ig or CTLA4-Ig+EP1013 cohorts). Re-transplantation with third-party islets resulted in robust rejection in all recipients.