Evaluation of donor-specific transfusion sources: unique failure of bone marrow cells to induce prolonged skin allograft survival with anti-CD154 monoclonal antibody.
BACKGROUND
Treatment with anti-CD154 monoclonal antibody (mAb) plus a donor-specific transfusion (DST) of spleen cells prolongs skin allograft survival in mice through a mechanism involving deletion of host alloreactive CD8(+) T cells. It is unknown if other lymphohematopoietic cell populations can be used as a DST.


METHODS
Murine recipients of allogeneic skin grafts on day 0 were either untreated or given a DST on day -7 plus 4 doses of anti-CD154 mAb on days -7, -4, 0, and +4. Deletion of CD8(+) alloreactive cells was measured using "synchimeric" CBA recipients, which circulate trace populations of TCR transgenic alloreactive CD8(+) T cells.


RESULTS
Transfusion of splenocytes, thymocytes, lymph node cells, or buffy coat cells led to prolonged skin allograft survival in recipients treated with anti-CD154 mAb. In contrast, bone marrow DST failed to delete host alloreactive CD8(+) T cells and was associated with brief skin allograft survival. Transfusions consisting of bone marrow-derived dendritic cells or a mixture of splenocytes and bone marrow cells were also ineffective.


CONCLUSIONS
Donor-specific transfusions of splenocytes, thymocytes, lymph node cells, or buffy coat cells can prolong skin allograft survival in recipients treated with costimulation blockade. Bone marrow cells fail to serve this function, in part by failing to delete host alloreactive CD8(+) T cells, and they may actively interfere with the function of a spleen cell DST. The data suggest that transplantation tolerance induction protocols that incorporate bone marrow cells to serve as a DST may not be effective.
Markees
Thomas G
TG
Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Pearson
Todd
T
Cuthbert
Amy
A
Pearson
Andrea L
AL
Shultz
Leonard D
LD
Leif
Jean
J
Phillips
Nancy E
NE
Mordes
John P
JP
Greiner
Dale L
DL
Rossini
Aldo A
AA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001803:Blood Transfusion; D001854:Bone Marrow Cells / Q000502:physiology*; D023201:CD40 Ligand / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000637:transplantation; D006085:Graft Survival; D008212:Lymphocyte Depletion; D008793:Metrizamide / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D016038:Skin Transplantation; D013154:Spleen / Q000166:cytology; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D023201:CD40 Ligand; D008793:Metrizamide