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Titel: Effect of everolimus-based drug regimens on CMV-specific T-cell functionality after renal transplantation: 12-month ATHENA subcohort-study results
VerfasserIn: Hauser, Ingeborg A.
Marx, Stefanie
Sommerer, Claudia
Suwelack, Barbara
Dragun, Duska
Witzke, Oliver
Lehner, Frank
Schiedel, Christiane
Porstner, Martina
Thaiss, Friedrich
Neudörfl, Christine
Falk, Christine S.
Nashan, Björn
Sester, Martina
Sprache: Englisch
Titel: European Journal of Immunology
Bandnummer: 51
Heft: 4
Seiten: 943–955
Verlag/Plattform: Wiley
Erscheinungsjahr: 2020
Freie Schlagwörter: CMV
CD4 T cells
CTLA-4
Everolimus
PD-1
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Post-transplant cytomegalovirus (CMV) infections and increased viral replication are associated with CMV-specific T-cell anergy. In the ATHENA-study, de-novo everolimus (EVR) with reduced-exposure tacrolimus (TAC) or cyclosporine (CyA) showed significant benefit in preventing CMV infections in renal transplant recipients as compared to standard TAC + mycophenolic acid (MPA). However, immunomodulatory mechanisms for this effect remain largely unknown. Ninety patients from the ATHENA-study completing the 12-month visit on-treatment (EVR + TAC n = 28; EVR + CyA n = 19; MPA + TAC n = 43) were included in a posthoc analysis. Total lymphocyte subpopulations were quantified. CMV-specific CD4 T cells were determined after stimulation with CMV-antigen, and cytokine-profiles and various T-cell anergy markers were analyzed using flow cytometry. While 25.6% of MPA + TAC-treated patients had CMV-infections, no such events were reported in EVR-treated patients. Absolute numbers of lymphocyte subpopulations were comparable between arms, whereas the percentage of regulatory T cells was significantly higher with EVR + CyA versus MPA + TAC (p = 0.019). Despite similar percentages of CMV-specific T cells, their median expression of CTLA-4 and PD-1 was lower with EVR + TAC (p < 0.05 for both) or EVR + CyA (p = 0.045 for CTLA-4) compared with MPA + TAC. Moreover, mean percentages of multifunctional CMV-specific T cells were higher with EVR + TAC (27.2%) and EVR + CyA (29.4%) than with MPA + TAC (19.0%). In conclusion, EVR-treated patients retained CMV-specific T-cell functionality, which may contribute to enhanced protection against CMV infections.
DOI der Erstveröffentlichung: 10.1002/eji.202048855
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-353605
hdl:20.500.11880/32268
http://dx.doi.org/10.22028/D291-35360
ISSN: 1521-4141
0014-2980
Datum des Eintrags: 1-Feb-2022
Bezeichnung des in Beziehung stehenden Objekts: Supporting Information
In Beziehung stehendes Objekt: https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Feji.202048855&file=eji4963-sup-0001-SuppMat.docx
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Infektionsmedizin
Professur: M - Prof. Dr. Martina Sester
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes



Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons Creative Commons