BKV Clearance Time Correlates With Exhaustion State and T-Cell Receptor Repertoire Shape of BKV-Specific T-Cells in Renal Transplant Patients
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...
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Frontiers Media S.A.
2019-04-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00767/full |
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doaj-aa141ddb2d404f9cb20525cada542474 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ulrik Stervbo Ulrik Stervbo Mikalai Nienen Mikalai Nienen Mikalai Nienen Benjamin J. D. Weist Leon Kuchenbecker Jochen Hecht Jochen Hecht Patrizia Wehler Timm H. Westhoff Petra Reinke Petra Reinke Nina Babel Nina Babel |
spellingShingle |
Ulrik Stervbo Ulrik Stervbo Mikalai Nienen Mikalai Nienen Mikalai Nienen Benjamin J. D. Weist Leon Kuchenbecker Jochen Hecht Jochen Hecht Patrizia Wehler Timm H. Westhoff Petra Reinke Petra Reinke Nina Babel Nina Babel BKV Clearance Time Correlates With Exhaustion State and T-Cell Receptor Repertoire Shape of BKV-Specific T-Cells in Renal Transplant Patients Frontiers in Immunology BKV T-cell TCR repertoire exhaustion diversity immunology |
author_facet |
Ulrik Stervbo Ulrik Stervbo Mikalai Nienen Mikalai Nienen Mikalai Nienen Benjamin J. D. Weist Leon Kuchenbecker Jochen Hecht Jochen Hecht Patrizia Wehler Timm H. Westhoff Petra Reinke Petra Reinke Nina Babel Nina Babel |
author_sort |
Ulrik Stervbo |
title |
BKV Clearance Time Correlates With Exhaustion State and T-Cell Receptor Repertoire Shape of BKV-Specific T-Cells in Renal Transplant Patients |
title_short |
BKV Clearance Time Correlates With Exhaustion State and T-Cell Receptor Repertoire Shape of BKV-Specific T-Cells in Renal Transplant Patients |
title_full |
BKV Clearance Time Correlates With Exhaustion State and T-Cell Receptor Repertoire Shape of BKV-Specific T-Cells in Renal Transplant Patients |
title_fullStr |
BKV Clearance Time Correlates With Exhaustion State and T-Cell Receptor Repertoire Shape of BKV-Specific T-Cells in Renal Transplant Patients |
title_full_unstemmed |
BKV Clearance Time Correlates With Exhaustion State and T-Cell Receptor Repertoire Shape of BKV-Specific T-Cells in Renal Transplant Patients |
title_sort |
bkv clearance time correlates with exhaustion state and t-cell receptor repertoire shape of bkv-specific t-cells in renal transplant patients |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-04-01 |
description |
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. |
topic |
BKV T-cell TCR repertoire exhaustion diversity immunology |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.00767/full |
work_keys_str_mv |
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doaj-aa141ddb2d404f9cb20525cada5424742020-11-25T00:34:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-04-011010.3389/fimmu.2019.00767389717BKV Clearance Time Correlates With Exhaustion State and T-Cell Receptor Repertoire Shape of BKV-Specific T-Cells in Renal Transplant PatientsUlrik Stervbo0Ulrik Stervbo1Mikalai Nienen2Mikalai Nienen3Mikalai Nienen4Benjamin J. D. Weist5Leon Kuchenbecker6Jochen Hecht7Jochen Hecht8Patrizia Wehler9Timm H. Westhoff10Petra Reinke11Petra Reinke12Nina Babel13Nina Babel14Center for Translational Medicine, Medical Clinic I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, GermanyBerlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyBerlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyInstitute for Medical Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyLabor Berlin-Charité Vivantes GmbH, Berlin, GermanyBerlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyApplied Bioinformatics, Center for Bioinformatics Tübingen, University of Tübingen, Tübingen, GermanyCentre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, SpainUniversitat Pompeu Fabra, Barcelona, SpainBerlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyCenter for Translational Medicine, Medical Clinic I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, GermanyBerlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyBerlin Center for Advanced Therapies, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyCenter for Translational Medicine, Medical Clinic I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, GermanyBerlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyReactivation 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.00767/fullBKVT-cellTCR repertoireexhaustiondiversityimmunology |