Use of mobilized peripheral blood stem cells (mPBSC) for the induction of mixed chimerism and tolerance / Zvonimir Koporc
VerfasserKoporc, Zvonimir
Begutachter / BegutachterinKubicek, P. Christian ; Wekerle, Thomas
Umfang159 Bl. : graph. Darst.
HochschulschriftWien, Techn. Univ., Diss., 2006
Zsfassung in dt. Sprache
Bibl. ReferenzOeBB
Schlagwörter (EN)mobilized peripheral blood stem cells (mPBSC)/ mixed chimerism / tolerance
Schlagwörter (GND)Blutstammzelle / Chimäre <Biologie> / Toleranz <Biologie>
URNurn:nbn:at:at-ubtuw:1-14145 Persistent Identifier (URN)
 Das Werk ist frei verfügbar
Use of mobilized peripheral blood stem cells (mPBSC) for the induction of mixed chimerism and tolerance [2.8 mb]
Zusammenfassung (Deutsch)

Allogeneic bone marrow transplantation (BMT) under costimulation blockade allows induction of mixed chimerism and tolerance without global T cell depletion. The mildest such protocols without recipient cytoreduction, however, require clinically impracticable BM doses. The successful use of mobilized peripheral blood stem cells (PBSC) instead of BM in such regimens would provide a substantial advance, allowing transplantation of higher doses of hematopoietic donor cells. We thus transplanted fully allogeneic murine granulocyte colony-stimulating-factor (G-CSF) mobilized PBSC under costimulation blockade (anti-CD154 and CTLA4Ig). Unexpectedly, PBSC did not engraft, even when very high cell doses and non-myeloablative total body irradiation (TBI) were used. Paradoxically, T cells contained in the donor PBSC triggered rejection of the transplanted donor cells.

Donor-specific transfusion and transient immunosuppression prevented PBSC-triggered rejection and mixed chimerism and tolerance were achieved, but graft-versus-host disease (GVHD) occurred. The combination of in vivo T cell depletion with costimulation blockade prevented rejection and GVHD. Thus, if allogeneic PBSC are transplanted instead of BMC costimulation blockade alone did not induce chimerism and tolerance without unacceptable GVHD-toxicity, and the addition of global T cell depletion was required for success.