Cutting Edge: Immunological consequences and trafficking of human regulatory macrophages administered to renal transplant recipients.

Hutchinson, James A; Riquelme, Paloma; Sawitzki, Birgit; Tomiuk, Stefan; Miqueu, Patrick; Zuhayra, Maaz; Oberg, Hans H; Pascher, Andreas; Lützen, Ulf; Janssen, Uwe; Broichhausen, Christiane; Renders, Lutz; Thaiss, Friedrich; Scheuermann, Ernst; Henze, Eberhard; Volk, Hans-Dieter; Chatenoud, Lucienne; Lechler, Robert I; Wood, Kathryn J; Kabelitz, Dieter; Schlitt, Hans J; Geissler, Edward K; Fändrich, Fred

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.