Low-dose cyclosporine mediates donor hyporesponsiveness in a fully mismatched rat kidney transplant model

Department of Visceral, Transplantation and Thoracic Surgery, Medizinische Universitaet Innsbruck, Austria
Transplant Immunology (Impact Factor: 1.46). 03/2012; 26(4):176-85. DOI: 10.1016/j.trim.2012.02.004
Source: PubMed


Tolerance induction protocols have been successfully tested in animal models, yet their compatibility with immunosuppressive drugs remains to be fully elucidated. Our own previous data have indicated that cyclosporine A (CsA) affects the balance of effector and regulatory mechanisms with low-dose CsA doses promoting hyporesponsiveness. Here, we present a fully mismatched rat kidney model in which low-dose CsA treatment induces donor hyporesponsiveness to secondary renal allografts. Lewis recipients of DA kidney grafts received low, medium or high doses of CsA × 10 days. By 30 days, the primary transplant was removed and a second transplant of donor origin was engrafted. Following low-dose CsA, but not high-dose CsA treatment of the primary recipient, secondary transplants were accepted long-term in the absence of immunosuppression. Regulatory T-cell function was unimpaired and independent of the CyA dosage. Of note, low-dose CsA significantly reduced alloantibody titers in primary recipients. Adoptive transfer of graft infiltrating cells or splenocytes from hyporesponsive recipients supported long-term acceptance of donor kidney allografts. These results demonstrate a dose-dependent and transferable "pro-tolerogenic" effect of low-dose CsA treatment. This model is of clinical relevance to test the interference of CsA with tolerance induction in the absence of additional immunosuppression.

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Available from: Anja Reutzel-Selke, Dec 17, 2013
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