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
2019-06-06T11:30:21Z
dc.date.available
2019-06-06T11:30:21Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/24694
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-2454
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.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
TCR repertoire
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
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
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
767
dcterms.bibliographicCitation.doi
10.3389/fimmu.2019.00767
dcterms.bibliographicCitation.journaltitle
Frontiers in Immunology
dcterms.bibliographicCitation.originalpublishername
Frontiers Media S.A.
dcterms.bibliographicCitation.volume
10
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
31024575
dcterms.isPartOf.issn
1664-3224