Acute and Chronic Vascular Rejection in Nonhuman Primate Kidney Transplantation
Article first published online: 23 MAR 2006
American Journal of Transplantation
Volume 6, Issue 6, pages 1285–1296, June 2006
How to Cite
Wieczorek, G., Bigaud, M., Menninger, K., Riesen, S., Quesniaux, V., Schuurman, H.-J., Audet, M., Blancher, A., Mihatsch, M. J. and Nickeleit, V. (2006), Acute and Chronic Vascular Rejection in Nonhuman Primate Kidney Transplantation. American Journal of Transplantation, 6: 1285–1296. doi: 10.1111/j.1600-6143.2006.01307.x
- Issue published online: 23 MAR 2006
- Article first published online: 23 MAR 2006
- Received 7 June 2005, revised 19 January 2006 and accepted for publication 24 January 2006
- Allograft rejection;
- kidney transplantation;
- nonhuman primate;
- vascular rejection
A nonhuman primate (NHP) study was designed to evaluate in nonlife-supporting kidney allografts the progression from acute rejection with transplant endarteritis (TXA) to chronic rejection (CR) with sclerosing vasculopathy. Group G1 (n = 6) received high cyclosporine A (CsA) immunosuppression and showed neither TXA nor CR during 90 days post-transplantation. Group G2 (n = 6) received suboptimal CsA immunosuppression and showed severe TXA with graft loss within 46 days (median). Arterial intimal changes included infiltration of macrophages and T lymphocytes (CD3, CD4, CD8) with few myofibroblasts, abundant fibronectin/collagen IV, scant collagens I/III, high rate of cellular proliferation and no C4d accumulation along peritubular capillaries. Group G3 (n = 12) received suboptimal CsA and anti-rejection therapy (rabbit ATG + methylprednisolone + CsA) of TXA. Animals developed CR and lost grafts within 65 days (median). As compared to G2, the arterial intimal changes showed less macrophages and T lymphocytes, an increased number of myofibroblasts, abundant fibronectin/collagen IV and scar collagens I/III, C4d deposition along capillaries in 60% of animals and transplant glomerulopathy in 80% of animals.
In conclusion, CR is an immune stimulated process initiated during TXA with the accumulation and proliferation of myofibroblasts, and progressive deposition of collagens in the intima. Our experimental design appears well suited to study events leading to CR.