Jensen KP, Hongo DA, Ji X, et al. Development of Immunosuppressive Myeloid Cells to Induce Tolerance in Solid Organ and Hematopoietic Cell Transplant Recipients. Blood Advances. 2021; 5 (17): 3290 (doi: 10.1182/bloodadvances.2020003669). Researchers say immunosuppressive polymorphonuclear (pmn) myeloid-derived suppressor cells (MDSCs) likely are required to achieve immune tolerance after living donor kidney transplantation and hematopoietic cell transplant. Using a conditioning protocol designed to establish mixed chimerism and tolerance in mice, clinical trials demonstrated similar immunological changes in humans. The regimen — which entailed total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) conditioning — resulted in substantial depletion of recipient T cells and a spike in MDSCs in patient blood following transplantation. These post-procedure MDSCs had increased immunosuppressive function, and effectively blocked the activation, proliferation, and production of inflammatory cytokines by pretransplant T cells. Immune tolerance, defined by complete discontinuation of immunosuppressive drugs, was reached in both HLA-matched and -mismatched patients. At 14-year follow-up, investigators found fewer than 5% of patients enrolled in the TLI-ATG tolerance regimen suffered kidney graft loss due to rejection.