Rapamycin and CTLA4Ig synergize to induce stable mixed chimerism without the need for CD40 blockade

N. Pilat, C. Klaus, C. Schwarz, K. Hock, R. Oberhuber, E. Schwaiger, M. Gattringer, H. Ramsey, U. Baranyi, B. Zelger, G. Brandacher, F. Wrba, T. Wekerle

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


The mixed chimerism approach achieves donor-specific tolerance in organ transplantation, but clinical use is inhibited by the toxicities of current bone marrow (BM) transplantation (BMT) protocols. Blocking the CD40:CD154 pathway with anti-CD154 monoclonal antibodies (mAbs) is exceptionally potent in inducing mixed chimerism, but these mAbs are clinically not available. Defining the roles of donor and recipient CD40 in a murine allogeneic BMT model, we show that CD4 or CD8 activation through an intact direct or CD4 T cell activation through the indirect pathway is sufficient to trigger BM rejection despite CTLA4Ig treatment. In the absence of CD4 T cells, CD8 T cell activation via the direct pathway, in contrast, leads to a state of split tolerance.

Original languageEnglish (US)
Pages (from-to)1568-1579
Number of pages12
JournalAmerican Journal of Transplantation
Issue number6
StatePublished - Jun 1 2015


  • Basic (laboratory) research / science
  • bone marrow / hematopoietic stem cell transplantation
  • immunobiology
  • tolerance: chimerism
  • tolerance: costimulation blockade
  • translational research / science

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)


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