Inhibition of Polyomavirus BK-Specific T-Cell Responses by Immunosuppressive Drugs

摘要: BACKGROUND: Reducing immunosuppression is the treatment of choice for polyomavirus-associated nephropathy in kidney transplant (KT) patients, but strategies and targets are uncertain. METHODS: Using interferon-gamma ELISpot assays, we investigated immunosuppressive drug levels polyomavirus BK (BKV) large T-antigen-specific T-cell responses KT patients vivo healthy donors after titrating vitro. RESULTS: In BKV-specific were inversely correlated with tacrolimus trough (R=0.28, P>0.002), not mycophenolate levels, prednisone, or overall dosing. vitro concentrations above 6 ng/mL inhibited BKV- cytomegalovirus-specific T-cells more than 50%, whereas less 30% inhibition was observed below 3 ng/mL. Inhibition by cyclosporine A 50% at 1920 960 ng/mL, corresponding to clinical C0 200 100 respectively. However, up 8 microg/mL, leflunomide 50 sirolimus 64 did inhibit production, antigen-dependent expansion. CONCLUSIONS: Calcineurin-inhibitor critical activation. calcineurin inhibitors should be considered as first step, conversion mTOR may an attractive alternative second step that validated BKV intervention trials.