Persistence of donor-derived protein in host myeloid cells after induced rejection of engrafted allogeneic bone marrow cells
Received 13 November 2009; received in revised form 15 January 2010; accepted 8 February 2010. published online 17 February 2010.
Objective
In recipients of allogeneic hematopoietic stem cell transplantation to treat hematologic malignancies, we have unexpectedly observed anti-tumor effects in association with donor cell rejection in both mice and humans. Host-type CD8 T cells were shown to be required for these anti-tumor effects in the murine model. Because sustained host CD8 T-cell activation was observed in the murine bone marrow following the disappearance of donor chimerism in the peripheral blood, we hypothesized that donor antigen presentation in the bone marrow might be prolonged.
Materials and Methods
To assess this hypothesis, we established mixed chimerism with green fluorescent protein (GFP)−positive allogeneic bone marrow cells, induced rejection of the donor cells by giving recipient leukocyte infusions, and utilized in vivo microscopy to follow GFP-positive cells.
Results
After peripheral donor leukocytes disappeared, GFP persisted within host myeloid cells surrounding the blood vessels in the bone marrow, suggesting that the host myeloid cells captured donor-derived GFP protein.
Conclusions
Because the host-vs-graft reaction promotes induction of anti-tumor responses in this model, this retention of donor-derived protein may play a role in the efficacy of recipient leukocyte infusions as an anti-tumor therapy.
aBone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, Mass., USA
bAdvanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Mass., USA
cHarvard Stem Cell Institute, Cambridge, Mass., USA
Offprint requests to: Megan Sykes, M.D., Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital/Harvard Medical School, MGH-East, Building 149-5102, 13th Street, Boston, MA 02129
∗ Drs. Saito and Fujisaki contributed equally to this work.
ABSTRACT