Evaluation of donor-specific transfusion sources: unique failure of bone marrow cells to induce prolonged skin allograft survival with anti-CD154 monoclonal antibody
Graduate School of Biomedical Sciences; Department of Medicine, Division of Diabetes; Department of Medicine, Division of Endocrinology and Metabolism
Medical Subject Headings
Animals; Antibodies, Monoclonal; *Blood Transfusion; Bone Marrow Cells; CD40 Ligand; CD8-Positive T-Lymphocytes; Dendritic Cells; *Graft Survival; Lymphocyte Depletion; Metrizamide; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred CBA; *Skin Transplantation; Spleen; Transplantation, Homologous
Life Sciences | Medicine and Health Sciences
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.
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Citation: Transplantation. 2004 Dec 15;78(11):1601-8.
Markees, Thomas G.; Pearson, Todd; Cuthbert, Amy; Pearson, Andrea L.; Shultz, Leonard D.; Leif, Jean H.; Phillips, Nancy E.; Mordes, John P.; Greiner, Dale L.; and Rossini, Aldo A., "Evaluation of donor-specific transfusion sources: unique failure of bone marrow cells to induce prolonged skin allograft survival with anti-CD154 monoclonal antibody" (2004). GSBS Student Publications. 807.