Costimulation blockade followed by a 12-week period of cyclosporine A facilitates prolonged drug-free survival of rhesus monkey kidney allografts

Costimulation blockade as a single immunosuppressive treatment modality is not sufficient to prevent graft rejection. Here, we report an induction therapy using antagonistic antibodies against CD40 and CD86, given twice weekly from day-1 until day 56, followed by a delayed 12-week course of low-dose cyclosporine A (CsA) treatment in the rhesus monkey kidney-allo graft model. Low-dose CsA treatment was initiated on day 42 and tapered until total cessation of all treatment on day 126. Treatment with anti-CD40/86 alone resulted in graft survival of 61, 71, 75, 78, and 116 days. Costimulation blockade followed by CsA resulted in more than 3-year drug-free survival in two of four animals. None of the animals developed donor-specific alloantibodies. Transforming growth factor-beta producing cells are present in early as well as in late kidney-graft biopsies and could play a role in the observed long-term drug-free graft survival.