Age and Latent Cytomegalovirus Infection Do Not Affect the Magnitude of De Novo SARS‐CoV‐2‐Specific CD8+ T Cell Responses
Jet van den Dijssel, Veronique A. L. Konijn, Mariël C Duurland, Rivka de Jongh, Lianne Koets, Barbera Veldhuisen, Hilde Raaphorst, Annelies W. Turksma, Julian J. Freen‐van Heeren, Maurice Steenhuis, Theo Rispens, C Ellen van der Schoot, S. Marieke van Ham, Rene A. W. van Lier, Klaas P. J. M. van Gisbergen, Anja ten Brinke, Carolien E. van de SandtABSTRACT
Immunosenescence, age‐related immune dysregulation, reduces immunity upon vaccinations and infections. Cytomegalovirus (CMV) infection results in declining naïve (Tnaïve) and increasing terminally differentiated (Temra) 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+ Tnaïve cells in older CMV‐ and CMV+ individuals. Robust SARS‐CoV‐2‐specific central memory CD8+ T (Tcm) 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 (Tscm), highest Temra and PD1+ populations, suggesting that age, not CMV, may impact long‐term SARS‐CoV‐2 immunity.