Publication:
In-Depth Profiling of T-Cell Responsiveness to Commonly Recognized CMV Antigens in Older People Reveals Important Sex Differences.

dc.contributor.authorReus, Bernhard
dc.contributor.authorCaserta, Stefano
dc.contributor.authorLarsen, Martin
dc.contributor.authorMorrow, George
dc.contributor.authorBano, Aalia
dc.contributor.authorHallensleben, Michael
dc.contributor.authorRajkumar, Chakravarthi
dc.contributor.authorPera, Alejandra
dc.contributor.authorKern, Florian
dc.contributor.funderThe Dunhill Medical Trust
dc.contributor.funderInstituto de Salud Carlos III
dc.contributor.funderERDF/ESF
dc.date.accessioned2023-02-09T11:49:53Z
dc.date.available2023-02-09T11:49:53Z
dc.date.issued2021-07-26
dc.description.abstractThe impact of biological sex on T-cell immunity to Cytomegalovirus (CMV) has not been investigated in detail with only one published study comparing CMV-specific T-cell responses in men and women. Many studies, however, have shown an association between CMV infection and immunosenescence, with broad effects on peripheral blood lymphocyte subsets as well as the T and B-cell repertoires. Here, we provide a detailed analysis of CMV-specific T-cell responses in (n=94) CMV+ older people, including 47 women and 47 men aged between 60 and 93 years. We explore sex differences with respect to 16 different CMV proteins arranged in 14 peptide pools (overlapping peptides). Following ex vivo stimulation, CD4 and CD8 T-cells producing IFN-γ, TNF, and IL-2 were enumerated by flow-cytometry (intracellular cytokine staining). T-cell responses were evaluated in terms of each cytokine separately or in terms of cytokines produced simultaneously (polyfunctionality). Surface memory phenotype and CD3 downmodulation were assessed in parallel. The polyfunctionality index and a memory subset differentiation score were used to identify associations between response size, cytokine production, polyfunctionality, and memory subset distribution. While no significant sex differences were found with respect to overall CMV target protein selection, the T-cell response in men appeared more focused and accompanied by a more prominent accumulation of CMV-specific memory CD4 and CD8 T-cells. T-cell polyfunctionality and differentiation were similar in the sexes, however, CMV-specific T-cells in men produced more pro-inflammatory cytokines. Particularly, TNF production by CD4 T-cells was stronger in men than in women. Also, compared with women, men had larger responses to CMV proteins with immediate-early/early kinetics than women, which might have been driven by CMV reactivation. In conclusion, the CMV-specific T-cell response in men was larger and more pro-inflammatory than in women. Our findings may help explain sex differences in CMV-associated pathologies.
dc.description.versionSi
dc.identifier.citationReus B, Caserta S, Larsen M, Morrow G, Bano A, Hallensleben M, et al. In-Depth Profiling of T-Cell Responsiveness to Commonly Recognized CMV Antigens in Older People Reveals Important Sex Differences. Front Immunol. 2021 Aug 13;12:707830
dc.identifier.doi10.3389/fimmu.2021.707830
dc.identifier.essn1664-3224
dc.identifier.pmcPMC8414256
dc.identifier.pmid34484207
dc.identifier.pubmedURLhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414256/pdf
dc.identifier.unpaywallURLhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.707830/pdf
dc.identifier.urihttp://hdl.handle.net/10668/18496
dc.journal.titleFrontiers in immunology
dc.journal.titleabbreviationFront Immunol
dc.language.isoen
dc.organizationInstituto Maimónides de Investigación Biomédica de Córdoba-IMIBIC
dc.page.number21
dc.provenanceRealizada la curación de contenido 03/09/2024
dc.publisherFrontiers Research Foundation
dc.pubmedtypeJournal Article
dc.pubmedtypeResearch Support, Non-U.S. Gov't
dc.relation.projectIDR278/0213
dc.relation.projectIDCP19/00008
dc.relation.publisherversionhttps://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.707830/full
dc.rightsAttribution 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectCytomegalovirus (CMV)
dc.subjectT cell
dc.subjectAging
dc.subjectBiological sex
dc.subjectImmunosenescence
dc.subject.decsAntígenos virales
dc.subject.decsCaracteres sexuales
dc.subject.decsCitomegalovirus
dc.subject.decsInfecciones por Citomegalovirus
dc.subject.decsInmunosenescencia
dc.subject.decsLinfocitos T CD4-positivos
dc.subject.decsLinfocitos T CD8-positivos
dc.subject.meshAged
dc.subject.meshAged, 80 and over
dc.subject.meshAntigens, Viral
dc.subject.meshCD4-Positive T-Lymphocytes
dc.subject.meshCD8-Positive T-Lymphocytes
dc.subject.meshCytomegalovirus
dc.subject.meshCytomegalovirus Infections
dc.subject.meshFemale
dc.subject.meshHumans
dc.subject.meshImmunosenescence
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshSex Characteristics
dc.titleIn-Depth Profiling of T-Cell Responsiveness to Commonly Recognized CMV Antigens in Older People Reveals Important Sex Differences.
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number12
dspace.entity.typePublication

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