Academic Journal

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

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: In-Depth Profiling of T-Cell Responsiveness to Commonly Recognized CMV Antigens in Older People Reveals Important Sex Differences
Συγγραφείς: Bernhard Reus, Stefano Caserta, Martin Larsen, George Morrow, Aalia Bano, Michael Hallensleben, Chakravarthi Rajkumar, Alejandra Pera, Florian Kern
Πηγή: Frontiers in Immunology, Vol 12 (2021)
Στοιχεία εκδότη: Frontiers Media S.A., 2021.
Έτος έκδοσης: 2021
Συλλογή: LCC:Immunologic diseases. Allergy
Θεματικοί όροι: aging, T cell, Cytomegalovirus (CMV), immunosenescence, biological sex, Immunologic diseases. Allergy, RC581-607
Περιγραφή: The 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.
Τύπος εγγράφου: article
Περιγραφή αρχείου: electronic resource
Γλώσσα: English
ISSN: 1664-3224
Relation: https://www.frontiersin.org/articles/10.3389/fimmu.2021.707830/full; https://doaj.org/toc/1664-3224
DOI: 10.3389/fimmu.2021.707830
Σύνδεσμος πρόσβασης: https://doaj.org/article/b951e00c673f46a0b439906d827a99e9
Αριθμός Καταχώρησης: edsdoj.b951e00c673f46a0b439906d827a99e9
Βάση Δεδομένων: Directory of Open Access Journals
Περιγραφή
ISSN:16643224
DOI:10.3389/fimmu.2021.707830