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

Christian Denecke, Anja Reutzel-Selke, Birgit Sawitzki, Olaf Boenisch, Zain I Khalpey, Martina Seifert, Johann Pratschke, Hans Dieter Volk, Stefan G. Tullius

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)176-185
Number of pages10
JournalTransplant Immunology
Volume26
Issue number4
DOIs
StatePublished - Jun 2012
Externally publishedYes

Fingerprint

Cyclosporine
Tissue Donors
Transplants
Kidney
Immunosuppression
Allografts
Isoantibodies
Adoptive Transfer
Regulatory T-Lymphocytes
Immunosuppressive Agents
Therapeutics
Animal Models
Pharmaceutical Preparations

Keywords

  • Cyclosporine
  • Hyporesponsiveness
  • Immunosuppression
  • Kidney transplantation

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Transplantation

Cite this

Low-dose cyclosporine mediates donor hyporesponsiveness in a fully mismatched rat kidney transplant model. / Denecke, Christian; Reutzel-Selke, Anja; Sawitzki, Birgit; Boenisch, Olaf; Khalpey, Zain I; Seifert, Martina; Pratschke, Johann; Volk, Hans Dieter; Tullius, Stefan G.

In: Transplant Immunology, Vol. 26, No. 4, 06.2012, p. 176-185.

Research output: Contribution to journalArticle

Denecke, C, Reutzel-Selke, A, Sawitzki, B, Boenisch, O, Khalpey, ZI, Seifert, M, Pratschke, J, Volk, HD & Tullius, SG 2012, 'Low-dose cyclosporine mediates donor hyporesponsiveness in a fully mismatched rat kidney transplant model', Transplant Immunology, vol. 26, no. 4, pp. 176-185. https://doi.org/10.1016/j.trim.2012.02.004
Denecke, Christian ; Reutzel-Selke, Anja ; Sawitzki, Birgit ; Boenisch, Olaf ; Khalpey, Zain I ; Seifert, Martina ; Pratschke, Johann ; Volk, Hans Dieter ; Tullius, Stefan G. / Low-dose cyclosporine mediates donor hyporesponsiveness in a fully mismatched rat kidney transplant model. In: Transplant Immunology. 2012 ; Vol. 26, No. 4. pp. 176-185.
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