BKV clearance time correlates with exhaustion state and T-cell receptor repertoire shape of BKV-specific T-cells in renal transplant patients

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• dc.contributor.author Stervbo, Ulrik
• dc.contributor.author Nienen, Mikalai
• dc.contributor.author Weist, Benjamin J. D.
• dc.contributor.author Kuchenbecker, Leon
• dc.contributor.author Hecht, Jochen
• dc.contributor.author Wehler, Patrizia
• dc.contributor.author Westhoff, Timm H.
• dc.contributor.author Reinke, Petra
• dc.contributor.author Babel, Nina
• dc.date.accessioned 2019-07-16T09:27:31Z
• dc.date.available 2019-07-16T09:27:31Z
• dc.date.issued 2019
• dc.description.abstract 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, which factors determine the duration of viral infection clearance remains so far unclear. Here we apply a combination of in-depth multi-parametric flow cytometry and NGS-based CDR3 beta chain receptor repertoire analysis of BKV-specific T-cells to a cohort of 7 kidney transplant patients during the clinical course of BKV reactivation. This way we followed TCR repertoires at single clone levels and functional activity of BKV-specific T-cells during the resolution of BKV infection. The duration of BKV clearance did not depend on the number of peripheral blood BKV-specific T-cells nor on a few immunodominant BKV-specific T-cell clones. Rather, the T-cell receptor repertoire diversity and exhaustion status of BKV-specific T-cells affected the duration of viral clearance: high clonotype diversity and lack of PD1 and TIM3 exhaustion markers on BKV-specific T-cells was associated with short clearance time. Our data thus demonstrate how the diversity and the exhaustion state of the T-cells can determine the clinical course of BKV infection.
• dc.description.sponsorship This work was supported by the grants e:KID from BMBF and OsteoSys from EFRE
• dc.format.mimetype application/pdf
• dc.identifier.citation Stervbo U, Nienen M, Weist BJD, Kuchenbecker L, Hecht J6, Wehler P et al. BKV clearance time correlates with exhaustion state and T-cell receptor repertoire shape of BKV-specific T-cells in renal transplant patients. Front Immunol. 2019 Apr 10;10:767. DOI: 10.3389/fimmu.2019.00767
• dc.identifier.doi http://dx.doi.org/10.3389/fimmu.2019.00767
• dc.identifier.issn 1664-3224
• dc.identifier.uri http://hdl.handle.net/10230/42006
• dc.language.iso eng
• dc.publisher Frontiers Media
• dc.relation.ispartof Frontiers in Immunology. 2019 Apr 10;10:767
• dc.rights © 2019 Stervbo, Nienen, Weist, Kuchenbecker, Hecht, Wehler, Westhoff, Reinke and Babel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• dc.subject.other Ronyons -- Trasplantació
• dc.subject.other Sistema immunològic
• dc.subject.other Genètica
• dc.subject.other Infecció
• dc.title BKV clearance time correlates with exhaustion state and T-cell receptor repertoire shape of BKV-specific T-cells in renal transplant patients
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion