Reactivation of the BK polyomavirus is known to lead to severe complications in kidney transplant patients. The current treatment strategy relies on decreasing the immunosuppression to allow the immune system to clear the virus. Recently we demonstrated a clear association between the resolution of BKV reactivation and reconstitution of BKV-specific CD4+ T-cells. However, the factors determining the duration of the clearance of the viral infection remain unknown. Here we apply a combination of in-depth multiparametric flow cytometry and CDR3 beta chain receptor repertoire analysis of BKV specific T-cells to a cohort of 5 kidney transplant patients with BKV reactivation. This allowed us to track the TCR repertoires at single clone levels during the clinical course of BKV infection. The number of BKV-specific T-cells in peripheral blood did not affect the duration of BKV infection. In contrast, the diversity of the T-cell receptor repertoire as well as exhaustion status of BKV-specific T-cells correlated with the duration of viral clearance. This duration was further found to be independent of hyperexpanded, immunodominant BKV-specific T-cell clones and of the overall magnitude of cellular immunity. Rather, the diversity of BKV-specific TCR repertoire in peripheral blood: high diversity of the repertoire and lack of PD1 and TIM-3 exhaustion markers on BKV-specific T-cells is associated with short remission time. Our data demonstrate that the quality (exhaustion status and shape of the repertoire) rather than quantity of BKV-specific T-cells determines the remission time after BKV reactivation.

CITATION INFORMATION: Stervbo U, Nienen M, Weist B, Wehler P, Westhoff T, Volk H.-D, Reinke P, Babel N. BKV Clearance Time Correlates with T-Cell Receptor Repertoire Shape and Exhaustion State of BKV-Specific T-Cells in Renal Transplant Patients with Severe BKV Infection. Am J Transplant. 2017;17 (suppl 3).

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