Abstract
Several types of myeloid suppressor cell are currently being developed as cell-based immunosuppressive agents. Despite detailed knowledge about the molecular and cellular functions of these cell types, expert opinions differ on how to best implement such therapies in solid organ transplantation. Efforts in our laboratory to develop a cell-based medicinal product for promoting tolerance in renal transplant patients have focused on a type of suppressor macrophage, which we call the regulatory macrophage (M reg). Our favoured clinical strategy is to administer donor-derived M regs to recipients one week prior to transplantation. In contrast, many groups working with tolerogenic dendritic cells (DCs) advocate post-transplant administration of recipient-derived cells. A third alternative, using myeloid-derived suppressor cells, presumably demands that cells are given around the time of transplantation, so that they can infiltrate the graft to create a suppressive environment. On present evidence, it is not possible to say which cell type and treatment strategy might be clinically superior. This review seeks to position our basic scientific and early-stage clinical studies of human regulatory macrophages within the broader context of myeloid suppressor cell therapy in transplantation.
Highlights
The existence of anti-inflammatory T cell-suppressive cells of the myeloid lineage has long been recognised and the ability of such cells to induce tolerance to autoand allo-antigens after adoptive transfer has been studied extensively
Patients MM and CA Since the TAIC-I and TAIC-II clinical trials, we have arrived at a detailed understanding of the derivation, phenotype and T cell-suppressive functions of in vitroderived human regulatory macrophages
Is low-dose tacrolimus monotherapy difficult to achieve in renal transplant recipients? Shapiro’s 2003 study remains a benchmark trial of minimised tacrolimus monotherapy in renal transplant recipients [65]. 150 patients were treated with 5 mg/kg anti-thymocyte globulin (ATG) and bolus prednisone as an induction therapy, and were subsequently maintained tacrolimus monotherapy, which was minimised in a step-wise fashion over many months (Figure 6)
Summary
The existence of anti-inflammatory T cell-suppressive cells of the myeloid lineage has long been recognised and the ability of such cells to induce tolerance to autoand allo-antigens after adoptive transfer has been studied extensively. We cannot say which cell type or clinical approach represents an optimal therapy; based on our preclinical animal studies and the outcomes of the TAIC-I and TAIC-II clinical trials, our research group favours the preoperative administration of donor-derived M regs. Patients MM and CA Since the TAIC-I and TAIC-II clinical trials, we have arrived at a detailed understanding of the derivation, phenotype and T cell-suppressive functions of in vitroderived human regulatory macrophages This knowledge has inspired methodological advances in regulatory macrophage manufacture, leading to a far purer and more homogeneous cell product, which has been applied to two further living-donor renal transplant recipients with encouraging results [3]. Estimation of the frequency of CNI monotherapy patients in the general transplant population with the tolerance signature
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