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Age and Latent Cytomegalovirus Infection Do Not Affect the Magnitude of De Novo SARS‐CoV‐2‐Specific CD8 + T Cell Responses

Year: 2025

Type: article

Abstract: ABSTRACT Immunosenescence, age‐related immune dysregulation, reduces immunity upon vaccinations and infections. Cytomegalovirus (CMV) infection results in declining naïve (T naïve ) and increasing terminally differentiated (T emra ) T cell populations, further aggravating immune aging. Both immunosenescence and CMV have been speculated to hamper the formation of protective T‐cell immunity against novel or emerging pathogens. The SARS‐CoV‐2 pandemic presented a unique opportunity to examine the impact of age and/or CMV on the generation of de novo SARS‐CoV‐2‐specific CD8 + T cell responses in 40 younger (22–40 years) and 37 older (50–66 years) convalescent individuals. Heterotetramer combinatorial coding combined with phenotypic markers were used to study 35 SARS‐CoV‐2 epitope‐specific CD8 + T cell populations directly ex vivo. Neither age nor CMV affected SARS‐CoV‐2‐specific CD8 + T cell frequencies, despite reduced total CD8 + T naïve cells in older CMV ‐ and CMV + individuals. Robust SARS‐CoV‐2‐specific central memory CD8 + T (T cm ) responses were detected in younger and older adults regardless of CMV status. Our data demonstrate that immune aging and CMV status did not impact the SARS‐CoV‐2‐specific CD8 + T cell response. However, SARS‐CoV‐2‐specific CD8 + T cells of older CMV ‐ individuals displayed the lowest stem cell memory (T scm ), highest T emra and PD1 + populations, suggesting that age, not CMV, may impact long‐term SARS‐CoV‐2 immunity.

Source: European Journal of Immunology

DOI: 10.1002/eji.202451565