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In-depth profiling of T-cell responsiveness to commonly recognized CMV antigens in older people reveals important sex differences
journal contribution
posted on 2023-06-10, 00:38 authored by Bernhard ReusBernhard Reus, Stefano Caserta, Martin Larsen, George Morrow, Aalia Bano, Michael Hallensleben, Chakravarthi RajkumarChakravarthi Rajkumar, Alejandra Pera, Florian KernFlorian KernThe 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-?, 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.
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- Published
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- Published version
Journal
Frontiers in ImmunologyISSN
1664-3224Publisher
Frontiers MediaExternal DOI
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12Page range
1-21Article number
a707830Department affiliated with
- Informatics Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2021-08-16First Open Access (FOA) Date
2021-08-16First Compliant Deposit (FCD) Date
2021-08-13Usage metrics
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