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-allograft 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.
Haanstra
Krista G
KG
Biomedical Primate Research Centre, 2288 GJ Rijswijk, The Netherlands.
Sick
Ella A
EA
Ringers
Jan
J
Wubben
Jacqueline A M
JA
Kuhn
Eva-Maria
EM
Boon
Louis
L
Jonker
Margreet
M
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D015703:Antigens, CD / Q000276:immunology; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000276:immunology; D013997:Time Factors; D014184:Transplantation, Homologous
D000906:Antibodies; D015703:Antigens, CD; D051940:B7-2 Antigen; D019013:CD40 Antigens; D008562:Membrane Glycoproteins