A cell-based approach to the minimization of immunosuppression in renal transplantation

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Abstract:

Summary

Five renal transplant recipients were preoperatively treated with transplant acceptance-inducing cells (TAICs) in a Phase-I safety study of TAICs as an adjunct immune-conditioning therapy in living-donor kidney transplantation. Initially, patients received anti-thymocyte globulin induction therapy in combination with tacrolimus and steroid immunosuppression. Over the course of 12 weeks, steroids were withdrawn and tacrolimus therapy was minimized. Three of the five patients were able to tolerate low-dose tacrolimus monotherapy and one patient was withdrawn from all immunosuppression for over 8 months. No acute or delayed adverse events were associated with the infusion of TAICs. Monitoring of the recipient anti-donor reactivity of TAIC-treated patients in mixed lymphocyte cultures demonstrated that, during periods of clinically stable graft function, recipient T-cell proliferation and cytokine secretion in response to stimulation with donor alloantigen was relatively suppressed. Therefore, although the TAIC-II trial did not provide conclusive evidence of a beneficial effect of preoperative TAIC treatment, the results were encouraging because they suggest that TAICs promote a state of alloantigen-specific unresponsiveness, which might allow safe minimization of pharmacological immunosuppression.

Keywords: TAIC; cell-based therapy; macrophage; tolerance; transplant

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1432-2277.2008.00692.x

Affiliations: 1:  Laboratory of Transplantation Research of the Clinic of General and Thoracic Surgery, University of Schleswig-Holstein, Kiel, Germany 2:  Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands 3:  Department of Nephrology, University Hospital of Düsseldorf, Düsseldorf, Germany 4:  Department of Nephrology, University Hospital of Duisburg-Essen, Essen, Germany 5:  Department of Nephrology, University of Schleswig-Holstein, Kiel, Germany 6:  Department of Haematology, University of Schleswig-Holstein, Kiel, Germany 7:  Institute of Immunology, University of Schleswig-Holstein, Kiel, Germany 8:  Division of Experimental Surgery, Department of Surgery, University of Regensburg, Regensburg, Germany

Publication date: August 1, 2008

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