10.14.21

Immunosuppressive Myeloid Cells for Tolerance in Solid Organ and HCT

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.

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