BACKGROUND: Costimulation blockade has been proposed to induce allograft tolerance. We combined an antagonist anti-CD40 monoclonal antibody (mAb) with an antagonist anti-CD86 mAb in a rhesus monkey kidney allograft model. We chose this combination because it leaves CD80-CD152 signaling unimpaired, allowing for the down-regulatory effect of CD152 signaling to take place through this pathway. METHODS: Rhesus monkeys underwent transplantation with a major histocompatibility complex-mismatched kidney. One group of animals received anti-CD40 alone, and a second group received the combination of anti-CD40 and anti-CD86, twice weekly for 56 days. RESULTS: Three animals with low levels of anti-CD40 rejected the transplanted kidney while still receiving treatment. Three animals with high levels of anti-CD40 rejected at days 91, 134, and 217 with signs of chronic rejection. Animals treated with the combination of anti-CD40 and anti-CD86 mAbs rejected their kidneys at days 61, 75, and 78, shortly after cessation of treatment. Two animals were killed on days 71 and 116 with a blocked ureter. These animals developed virtually no signs of tubulitis or infiltration during treatment and no donor-specific alloantibodies. CONCLUSIONS: Both treatment protocols prevented rejection for the duration of the treatment in most animals. Blocking costimulation by anti-CD40 or by anti-CD40 plus anti-CD86 may be an effective method to prevent graft rejection and may obviate the need for other immunosuppressive drugs, especially in the immediate posttransplantation period.
BACKGROUND: Costimulation blockade has been proposed to induce allograft tolerance. We combined an antagonist anti-CD40 monoclonal antibody (mAb) with an antagonist anti-CD86 mAb in a rhesus monkey kidney allograft model. We chose this combination because it leaves CD80-CD152 signaling unimpaired, allowing for the down-regulatory effect of CD152 signaling to take place through this pathway. METHODS:Rhesus monkeys underwent transplantation with a major histocompatibility complex-mismatched kidney. One group of animals received anti-CD40 alone, and a second group received the combination of anti-CD40 and anti-CD86, twice weekly for 56 days. RESULTS: Three animals with low levels of anti-CD40 rejected the transplanted kidney while still receiving treatment. Three animals with high levels of anti-CD40 rejected at days 91, 134, and 217 with signs of chronic rejection. Animals treated with the combination of anti-CD40 and anti-CD86 mAbs rejected their kidneys at days 61, 75, and 78, shortly after cessation of treatment. Two animals were killed on days 71 and 116 with a blocked ureter. These animals developed virtually no signs of tubulitis or infiltration during treatment and no donor-specific alloantibodies. CONCLUSIONS: Both treatment protocols prevented rejection for the duration of the treatment in most animals. Blocking costimulation by anti-CD40 or by anti-CD40 plus anti-CD86 may be an effective method to prevent graft rejection and may obviate the need for other immunosuppressive drugs, especially in the immediate posttransplantation period.
Authors: J Vermeiren; J L Ceuppens; H Haegel-Kronenberger; M De Boer; L Boon; S W Van Gool Journal: Clin Exp Immunol Date: 2004-02 Impact factor: 4.330
Authors: Ivana R Ferrer; Maylene E Wagener; Minqing Song; Allan D Kirk; Christian P Larsen; Mandy L Ford Journal: Proc Natl Acad Sci U S A Date: 2011-12-05 Impact factor: 11.205
Authors: Hayato Iwase; Burcin Ekser; Vikas Satyananda; Jay Bhama; Hidetaka Hara; Mohamed Ezzelarab; Edwin Klein; Robert Wagner; Cassandra Long; Jnanesh Thacker; Jiang Li; Hao Zhou; Maolin Jiang; Santosh Nagaraju; Huidong Zhou; Massimiliano Veroux; Pietro Bajona; Martin Wijkstrom; Yi Wang; Carol Phelps; Nikolai Klymiuk; Eckhard Wolf; David Ayares; David K C Cooper Journal: Xenotransplantation Date: 2015-04-03 Impact factor: 3.907
Authors: S C Kim; W Wakwe; L B Higginbotham; D V Mathews; C P Breeden; A C Stephenson; J Jenkins; E Strobert; K Price; L Price; R Kuhn; H Wang; A Yamniuk; S Suchard; A B Farris; T C Pearson; C P Larsen; M L Ford; A Suri; S Nadler; A B Adams Journal: Am J Transplant Date: 2017-02-25 Impact factor: 8.086