Monocytic myeloid-derived suppressor cells generated from rhesus macaque bone marrow enrich for regulatory T cells

Abstract

Putative monocytic myeloid-derived suppressor cells (mMDSC; lineageHLA-DR) were generated in 7-day cultures from normal rhesus macaque bone marrow (BM) cells in GM-CSF and IL-6. Three subsets were identified based on their differential expression of CD14, CD33, CD34 and CD11b. Following flow sorting, assessment of the capacity of these subsets to suppress anti-CD3/CD28-stimulated CD4 and CD8 T cell proliferation revealed that the most potent population was CD14CD33CD34CD11b. These BM-derived mMDSC markedly increased the incidence of CD4CD25CD127Foxp3 regulatory T cells in responder T cell populations. They offer potential value in testing the therapeutic efficacy of immunoregulatory mMDSC for the promotion of tolerance in nonhuman primate transplant models.

Regulatory dendritic cells for human organ transplantation

“…Patients receive SOC IS (MPA, steroid and tacrolimus), without Ab induction. Good manufacturing practice (GMP) grade DCreg are generated [81] in VitD3 and IL-10 from monocytes obtained by leukapheresis from prospective living organ donors, and infused as induction therapy into their respective recipients, 7 days before transplant. The DCreg dose range (2.5-10 × 10 6 /kg) corresponds to the range for which both safety and efficacy were demonstrated in the preclinical NHP renal transplant model [14].…”