Myeloid Derived Suppressor Cells Expand After Transplantation and their Augmentation Increases Graft Survival.

Myeloid derived suppressor cells (MDSC) expand in inflammatory microenvironment such as cancer and autoimmunity. To study if transplantation induces MDSC and these cells regulate allograft survival, C57BL/6 donor hearts were transplanted into BALB/c recipients and endogenous MDSC were characterized. The effects of adoptive transfer of transplant (tx), tumor (tm), and granulocyte-colony stimulating factor (gcsf)-expanded MDSCs or depletion of MDSC were assessed. MDSCs expanded after transplantation (1.7-4.6-fold) in the absence of immunosuppression, homed to allografts, and suppressed proliferation of CD4 T cells in vitro. Tx-MDSC differed phenotypically from tm-MDSC and gcsf-MDSC. Among various surface markers, Rae-1 expression was notably low and TGF-beta receptor II was high in tx-MDSC when compared to tm-MDSC and gcsf-MDSC. Adoptive transfer of these three MDSCs led to differential graft survival: control (6 days), tx-MDSC (7.5 days), tm-MDSC (9.5 days), and gcsf-MDSC (19.5 days). In combination with anti-CD154 mAb, MDSC synergistically extended graft survival from 40 days (anti-CD154 alone) to 86 days with tm-MDSC and 132 days with gcsf-MDSC. Early MDSC depletion (day 0 or 20), however, abrogated graft survival, but late depletion (day 25) did not. In conclusion, MDSCs expanded following transplantation, migrated to cardiac allografts, prolonged graft survival and were synergistic with anti-CD154 mAb.