Preliminary assessment of the feasibility of autologous myeloid-derived suppressor cell infusion in non-human primate kidney transplantation.

Myeloid-derived suppressor cells (MDSC) are a heterogenous population of immunosuppressive myeloid cells now considered important immune regulatory cells in diverse clinical conditions, including cancer, chronic inflammatory disorders and transplantation. In rodents, MDSC administration can inhibit graft-versus-host disease lethality and enhance organ or pancreatic islet allograft survival. There is also evidence, however, that under systemic inflammatory conditions, adoptively-transferred MDSC can rapidly lose their suppressive function. To our knowledge, there are no reports of autologous MDSC administration to either human or clinically-relevant non-human primate (NHP) transplant recipients. Monocytic (m) MDSC have been shown to be more potent suppressors of T cell responses than other subsets of MDSC. Following their characterization in rhesus macaques, we have conducted a preliminary analysis of the feasibility and preliminary efficacy of purified mMDSC infusion into MHC-mismatched rhesus kidney allograft recipients. The graft recipients were treated with rapamycin and the high affinity variant of the T cell co-stimulation blocking agent cytotoxic T lymphocyte antigen 4 Ig (Belatacept) that targets the B7-CD28 pathway. Graft survival and histology were not affected by infusions of autologous, leukapheresis product-derived mMDSC on days 7 and 14 post-transplant (cumulative totals of 3.19 and 1.98 × 10