Targeting the Kv1.3 potassium channel for immunosuppression in vascularized composite allotransplantation - A pilot study

Theresa Hautz, Christoph Krapf, Johanna Grahammer, Bettina Zelger, Tilman Hickethier, Christoph Seger, Nadine Eberhart, Christoph Wallner, Franka Messner, Katja Kotsch, Andrea Griesmacher, Gerald Brandacher, Wp Andrew Lee, Raimund Margreiter, Johann Pratschke, Hartmut Glossmann, Stefan Schneeberger

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Kv1.3-channels are critically involved in activation and function of effector memory T cells. Blocking Kv1.3-channels was investigated for its effect on skin rejection in a rat limb-transplantation-model. Animals received the Kv1.3-blocker correolide C systemically or locally as intra-graft-treatment in combination with tacrolimus. Systemic (intraperitoneal) administration of correolide C resulted in slight, but significant prolongation of allograft survival compared with untreated and placebo treated controls. In 4/6 correolide C treated animals, histology showed an intact epidermis and a mild infiltrate by day 10. High correolide C plasma trough levels correlated with prolonged allograft survival. A decrease in CD4+ and CD8+ effector memory T cells was observed in allograft skin, peripheral blood and the spleen on day 5. When applied subcutaneously in combination with systemic tacrolimus (30 days+/-anti-lymphocyte serum) detectable, but insignificant prolongation of graft survival was achieved. 2/5 animals showed an intact epidermis and a mild infiltrate until day 45. Tapering systemic tacrolimus and weaning on day 50 resulted in rejection by day 55, regardless of local correolide C treatment. Subcutaneous injection did not lead to systemic plasma levels. The Kv1.3-channel is a potential drug target worth exploring in more detail for immunosuppression in vascularized composite allotransplantation.

Original languageEnglish (US)
Pages (from-to)552-561
Number of pages10
JournalTransplant International
Volume26
Issue number5
DOIs
StatePublished - May 1 2013
Externally publishedYes

Keywords

  • Correolide C
  • Kv1.3 channel blocker
  • effector memory T cells
  • skin rejection
  • targeted therapy
  • vascularized composite allotransplantation

ASJC Scopus subject areas

  • Transplantation

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  • Cite this

    Hautz, T., Krapf, C., Grahammer, J., Zelger, B., Hickethier, T., Seger, C., Eberhart, N., Wallner, C., Messner, F., Kotsch, K., Griesmacher, A., Brandacher, G., Lee, W. A., Margreiter, R., Pratschke, J., Glossmann, H., & Schneeberger, S. (2013). Targeting the Kv1.3 potassium channel for immunosuppression in vascularized composite allotransplantation - A pilot study. Transplant International, 26(5), 552-561. https://doi.org/10.1111/tri.12080