Investigation of immunological approaches to enhance engraftment in a 1 Gy TBI canine hematopoietic stem cell transplantation model.
OBJECTIVE
Stable mixed hematopoietic chimerism can be established in a canine stem cell transplantation model using a conditioning consisting of total body irradiation (TBI; 2 Gy) and postgrafting immunosuppression with mycophenolate mofetil (MMF) and cyclosporin (CSA). Reduction of TBI had resulted previously in graft rejection in this model. We investigated whether postgrafting stimulation of donor T cells against recipient's hematopoietic antigens or graft augmentation with donor monocyte-derived dendritic cells (MoDC) promote engraftment following 1 Gy TBI.


METHODS
All dogs received dog leukocyte-antigen-identical bone marrow transplantation. Dogs were conditioned with either 2 Gy TBI (group 1) or 1 Gy TBI, followed by repetitive recipient hematopoietic cell lysate vaccinations (group 2) or graft augmentation with MoDC (group 3). Immunosuppression consisted of CSA and MMF.


RESULTS
In group 1, four animals remained stable chimeras for >110 weeks, and three rejected their grafts (week 10, week 14, week 16). All dogs in groups 2 and 3 rejected their graft (median: week 10 and 11, respectively). Peak chimerism and engraftment duration was shorter in the 1-Gy groups (p < 0.05) compared to group 1.


CONCLUSIONS
Neither postgrafting vaccination nor graft augmentation with MoDC were effective in supporting durable engraftment. Additional modifications are necessary to improve potential strategies aimed at establishment of early tissue specific graft-vs-host reactions.
Lange
Sandra
S
Division of Haematology/Oncology, Department of Medicine, University of Rostock, Rostock, Germany.
Altmann
Simone
S
Brandt
Bettina
B
Adam
Carsten
C
Riebau
Franziska
F
Vogel
Heike
H
Weirich
Volker
V
Hilgendorf
Inken
I
Storb
Rainer
R
Freund
Mathias
M
Junghanss
Christian
C
D000818:Animals; D004285:Dogs; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects* / Q000528:radiation effects*; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008954:Models, Biological; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid