[Background] Anergic T cells generated ex vivo under conditions of co-stimulatory blockade are reported to have tolerogenic effects. According this finding, we have conducted the clinical studies on induction of donor specific hyporesponsiveness in kidney transplantation (KTx) using adoptive transfer of self anergic cells. [Materials & Methods] The present study was performed in KTx recipients from HLA mismatched living donors. To obtain anergic cells, both recipient and donor received lymphocytapheresis 2 days before KTx, and 1 x 10¹⁰ and 5 x 10⁹ PBMCs were harvested respectively. Recipient's PBMCs were co-cultured with irradiated (30Gy) donor cells in the presence of anti CD80/CD86 mAb for 2 weeks. KTx was performed in a usual manner. Initial immunosuppression consists of CsA, MMF, and MP. As preconditioning, splenectomy or rituximab (200mg) + cyclophosphamide (CP, 20mg/kg x 2) were employed in the first series (group 1; n=12). In recent cases, rituximab + r-ATG (1.0mg/kg/day x 5) were administered instead of CP (group 2; n=4). Twelve days after KTx, the cultured cells were intravenously infused, after which immunosuppressants were gradually tapered. [Result] In the cultured cells, CD4, CD25, and FoxP3 expressions were upregulated. A series of procedure was safe and well tolerated in all the patients. Group 1 recipients showed excellent graft survival rate (100%) and function (mean serum Cr; 1.41mg/dl). Doses and blood concentration level of CsA and MMF were almost half of conventional KTx recipients, though high incidence of BPAR: 3 subclinical, 4 anti-rejection treatments, obliged us to discontinue further reducing immunosuppressant. In group 2, 4 patients (4 females; mean age 40.2 y; mean post-operative time 7.5 m) underwent KTx with modified regimen. Mean serum Cr levels were 1.32mg/dl. Although MLR are suppressed in a donor specific fashion, immunosuppressant reduction is still on the way. [Conclusions] These results showed that adoptive transfer of anergic cells could be one of promising approaches as tolerance-inducing strategy. However there seems to be a further necessity for modifying the regimen to achieve robust donor-specific hypo-responsiveness in clinical kidney transplantation.

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