{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T12:21:54Z","timestamp":1794313314516,"version":"4.9.0"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T00:00:00Z","timestamp":1609113600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Post\u2010transplant cytomegalovirus (CMV) infections and increased viral replication are associated with CMV\u2010specific T\u2010cell anergy. In the ATHENA\u2010study, de\u2010novo everolimus (EVR) with reduced\u2010exposure tacrolimus (TAC) or cyclosporine (CyA) showed significant benefit in preventing CMV infections in renal transplant recipients as compared to standard TAC\u00a0+\u00a0mycophenolic acid (MPA). However, immunomodulatory mechanisms for this effect remain largely unknown. Ninety patients from the ATHENA\u2010study completing the 12\u2010month visit on\u2010treatment (EVR\u00a0+\u00a0TAC n = 28; EVR\u00a0+\u00a0CyA n = 19; MPA\u00a0+\u00a0TAC n = 43) were included in a posthoc analysis. Total lymphocyte subpopulations were quantified. CMV\u2010specific CD4 T cells were determined after stimulation with CMV\u2010antigen, and cytokine\u2010profiles and various T\u2010cell anergy markers were analyzed using flow cytometry. While 25.6% of MPA\u00a0+\u00a0TAC\u2010treated patients had CMV\u2010infections, no such events were reported in EVR\u2010treated patients. Absolute numbers of lymphocyte subpopulations were comparable between arms, whereas the percentage of regulatory T cells was significantly higher with EVR +\u00a0CyA versus MPA\u00a0+\u00a0TAC (\n                    <jats:italic>p<\/jats:italic>\n                    = 0.019). Despite similar percentages of CMV\u2010specific T cells, their median expression of CTLA\u20104 and PD\u20101 was lower with EVR\u00a0+\u00a0TAC (\n                    <jats:italic>p\u00a0<\/jats:italic>\n                    &lt;\u00a00.05 for both) or EVR\u00a0+\u00a0CyA (\n                    <jats:italic>p<\/jats:italic>\n                    = 0.045 for CTLA\u20104) compared with MPA\u00a0+\u00a0TAC. Moreover, mean percentages of multifunctional CMV\u2010specific T cells were higher with EVR\u00a0+\u00a0TAC (27.2%) and EVR\u00a0+\u00a0CyA (29.4%) than with MPA\u00a0+\u00a0TAC (19.0%). In conclusion, EVR\u2010treated patients retained CMV\u2010specific T\u2010cell functionality, which may contribute to enhanced protection against CMV infections.\n                  <\/jats:p>","DOI":"10.1002\/eji.202048855","type":"journal-article","created":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T10:31:30Z","timestamp":1607682690000},"page":"943-955","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Effect of everolimus\u2010based drug regimens on CMV\u2010specific T\u2010cell functionality after renal transplantation: 12\u2010month ATHENA subcohort\u2010study results"],"prefix":"10.1002","volume":"51","author":[{"given":"Ingeborg A.","family":"Hauser","sequence":"first","affiliation":[{"name":"Department of Nephrology Goethe\u2010University Frankfurt  Frankfurt 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