Title: Use of mobilized peripheral blood stem cells (mPBSC) for the induction of mixed chimerism and tolerance
Language: English
Authors: Koporc, Zvonimir 
Qualification level: Doctoral
Keywords: mobilized peripheral blood stem cells (mPBSC); mixed chimerism; tolerance
Advisor: Kubicek, P. Christian 
Assisting Advisor: Wekerle, Thomas 
Issue Date: 2006
Number of Pages: 159
Qualification level: Doctoral
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.
URI: https://resolver.obvsg.at/urn:nbn:at:at-ubtuw:1-14145
Library ID: AC05031772
Organisation: E166 - Institut für Verfahrenstechnik, Umwelttechnik und Technische Biowissenschaften 
Publication Type: Thesis
Appears in Collections:Thesis

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