Transplant acceptance-inducing cells as an immune-conditioning therapy in renal transplantation

Abstract

Summary The transplant acceptance‐inducing cell (TAIC) is a type of immunoregulatory macrophage with the capacity to specifically dampen allogeneic rejection responses to a degree allowing safe minimization of conventional immunosuppressive therapy. In the first part of this report, the production and phenotype of the human TAIC is described. In the second part, an analysis is given of the TAIC‐I clinical trial, in which 12 recipients of renal transplants from deceased donors were treated with donor‐derived TAICs as an adjunct immune‐conditioning therapy. Conventional immunosuppression was gradually withdrawn from 10 of these 12 patients over a period of 8 weeks, starting in the fourth week after transplantation. All but two patients tolerated cessation of steroid therapy, while the remaining eight patients were first weaned from sirolimus and then, in six cases, were also weaned to low‐dose tacrolimus monotherapy. It is concluded that TAIC therapy is both safe and clinically practicable; however, the TAIC‐I trial was unable to provide evidence that postoperative TAIC administration has a beneficial effect.

Pathogenic and protective role of macrophages in kidney disease

“…Regulatory M⌽ possess anti-inflammatory and immune suppressive functions, which endow them with great potential for treating human kidney disease. Recently, a regulatory macrophage (Mreg) was generated in vitro by exposure of blood monocytes to M-CSF and IFN-␥ applied to patients undergoing kidney transplantation and appeared to be successful in reducing the dose of immunosuppressive drugs (28,29). Based on this pilot experience, a trial (The One Study; http://www.onestudy.org/) of M⌽ therapy in renal transplantation has commenced.…”

Cutting Edge: Immunological Consequences and Trafficking of Human Regulatory Macrophages Administered to Renal Transplant Recipients

“…Efforts in our laboratory to develop a cell product for promoting transplant tolerance in the clinical setting have focused on a type of suppressor macrophage, the human regulatory macrophage (M reg) (1)(2)(3)(4)(5)(6)(7). M regs exhibit a number of properties that might make them particularly suitable for clinical purposes, in particular, the cells are fully differentiated and potently T cell suppressive (8).…”

Tolerance in clinical transplantation: progress, challenge or just a dream?

“…In kidney allograft recipients, these regulatory macrophages (Mregs) induced a semi-stable state of alloantigen-specific graft acceptance which allowed for stable minimization of immunosuppressive drugs. Last year, two published reports focused on markers of tolerance [85,86,90]. A pattern of peripheral blood gene expression which correlates with a drug-free, tolerant state in kidney transplant recipients has been defined by two large collaborative networks, namely the multinational project called "Indices of Tolerance (IOT) as part of the RISET platform (funded by the 5th and 6th framework of the European Union), as an European counterpart of the US Immune Tolerance Network platform, ITN".…”

“…A recently published series of manuscripts describes this type of immunoregulatory macrophage for an autoimmune animal model of DSS-induced inflammatory bowel disease and in the setting of living-related and unrelated kidney transplantations [83][84][85][86][87][88][89][90]. In kidney allograft recipients, these regulatory macrophages (Mregs) induced a semi-stable state of alloantigen-specific graft acceptance which allowed for stable minimization of immunosuppressive drugs.…”