Cutting Edge: Immunological consequences and trafficking of human regulatory macrophages administered to renal transplant recipients.
Hutchinson JA., Riquelme P., Sawitzki B., Tomiuk S., Miqueu P., Zuhayra M., Oberg HH., Pascher A., Lützen U., Janssen U., Broichhausen C., Renders L., Thaiss F., Scheuermann E., Henze E., Volk H-D., Chatenoud L., Lechler RI., Wood KJ., Kabelitz D., Schlitt HJ., Geissler EK., Fändrich F.
Regulatory macrophages (M regs) were administered to two living-donor renal transplant recipients. Both patients were minimized to low-dose tacrolimus monotherapy within 24 wk of transplantation and subsequently maintained excellent graft function. After central venous administration, most M regs remained viable and were seen to traffic from the pulmonary vasculature via the blood to liver, spleen, and bone marrow. By 1 y posttransplantation, both patients displayed patterns of peripheral blood gene expression converging upon the IOT-RISET signature. Furthermore, both patients maintained levels of peripheral blood FOXP3 and TOAG-1 mRNA expression within the range consistent with nonrejection. It is concluded that M regs warrant further study as a potential immune-conditioning therapy for use in solid-organ transplantation. The results of this work are being used to inform the design of The ONE Study, a multinational clinical trial of immunomodulatory cell therapy in renal transplantation.