Prevention of kidney allograft rejection using anti-CD40 and anti-CD86 in primates
作者:
Krista Haanstra,
Jan Ringers,
Ella Sick,
Seema Ramdien-Murli,
Eva-Maria Kuhn,
Louis Boon,
Margreet Jonker,
期刊:
Transplantation
(OVID Available online 2003)
卷期:
Volume 75,
issue 5
页码: 637-643
ISSN:0041-1337
年代: 2003
出版商: OVID
数据来源: OVID
摘要:
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.
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