CTLA4Ig promotes the induction of hematopoietic chimerism and tolerance independently of indoleamine-2,3-dioxygenase

Ines Pree, Sinda Bigenzahn, Dietmar Fuchs, Zvonimir Koporc, Patrick Nierlich, Christiana Winkler, Gerald Brandacher, Megan Sykes, Ferdinand Muehlbacher, Felix Langer, Thomas Wekerle

Research output: Contribution to journalArticle

Abstract

Bone marrow transplantation (BMT) under costimulation blockade induces mixed chimerism and tolerance in rodent models. Recent data, predominantly from in vitro studies, suggest that in addition to blocking the CD28 costimulation pathway CTLA4Ig also acts through upregulating the tryptophan-catabolizing enzyme indoleamine-2,3-dioxygenase (IDO). Here we demonstrate that even though CTLA4Ig is critically required for the induction of chimerism and tolerance in a murine model of nonmyeloablative BMT, IDO activity is not. No significant differences were detectable in the kynurenine to tryptophan ratios (indicative of IDO activity) in sera of BMT recipients treated with CTLA4Ig (tolerant group) versus BMT recipients treated without CTLA4Ig (nontolerant group) versus naïve controls. In vivo inhibition of IDO immediately after BMT with CTLA4Ig or several months thereafter did not block achievement of chimerism and tolerance. Thus, IDO does not play a critical role in the induction or maintenance of chimerism and tolerance in a CTLA4Ig-based BMT model.

Original languageEnglish (US)
Pages (from-to)663-667
Number of pages5
JournalTransplantation
Volume83
Issue number5
DOIs
StatePublished - Mar 1 2007
Externally publishedYes

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Keywords

  • CTLA4Ig
  • Costimulation blockade
  • Indoleamine-2,3-dioxygenase
  • Mixed chimerism
  • Tolerance

ASJC Scopus subject areas

  • Transplantation

Cite this

Pree, I., Bigenzahn, S., Fuchs, D., Koporc, Z., Nierlich, P., Winkler, C., Brandacher, G., Sykes, M., Muehlbacher, F., Langer, F., & Wekerle, T. (2007). CTLA4Ig promotes the induction of hematopoietic chimerism and tolerance independently of indoleamine-2,3-dioxygenase. Transplantation, 83(5), 663-667. https://doi.org/10.1097/01.tp.0000255594.23445.29