tetano
Editor, Senior Moderator
Eur J Immunol
. 2025 Mar;55(3):e202451565.
doi: 10.1002/eji.202451565. Age and Latent Cytomegalovirus Infection Do Not Affect the Magnitude of De Novo SARS-CoV-2-Specific CD8[SUP]+[/SUP] T Cell Responses
Jet van den Dijssel[SUP] 1 2 [/SUP], Veronique A L Konijn[SUP] 1 2 [/SUP], Mariël C Duurland[SUP] 1 2 [/SUP], Rivka de Jongh[SUP] 1 2 [/SUP], Lianne Koets[SUP] 1 3 [/SUP], Barbera Veldhuisen[SUP] 1 4 [/SUP], Hilde Raaphorst[SUP] 5 [/SUP], Annelies W Turksma[SUP] 5 [/SUP], Julian J Freen-van Heeren[SUP] 5 [/SUP], Maurice Steenhuis[SUP] 1 [/SUP], Theo Rispens[SUP] 1 2 6 [/SUP], C Ellen van der Schoot[SUP] 1 [/SUP], S Marieke van Ham[SUP] 1 2 7 [/SUP], Rene A W van Lier[SUP] 8 [/SUP], Klaas P J M van Gisbergen[SUP] 1 2 9 [/SUP], Anja Ten Brinke[SUP] 1 2 [/SUP], Carolien E van de Sandt[SUP] 1 2 10 [/SUP]
Affiliations
Immunosenescence, age-related immune dysregulation, reduces immunity upon vaccinations and infections. Cytomegalovirus (CMV) infection results in declining naïve (T[SUB]naïve[/SUB]) and increasing terminally differentiated (T[SUB]emra[/SUB]) 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[SUP]+[/SUP] 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[SUP]+[/SUP] T cell populations directly ex vivo. Neither age nor CMV affected SARS-CoV-2-specific CD8[SUP]+[/SUP] T cell frequencies, despite reduced total CD8[SUP]+[/SUP] T[SUB]naïve[/SUB] cells in older CMV[SUP]-[/SUP] and CMV[SUP]+[/SUP] individuals. Robust SARS-CoV-2-specific central memory CD8[SUP]+[/SUP] T (T[SUB]cm[/SUB]) 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[SUP]+[/SUP] T cell response. However, SARS-CoV-2-specific CD8[SUP]+[/SUP] T cells of older CMV[SUP]-[/SUP] individuals displayed the lowest stem cell memory (T[SUB]scm[/SUB]), highest T[SUB]emra[/SUB] and PD1[SUP]+[/SUP] populations, suggesting that age, not CMV, may impact long-term SARS-CoV-2 immunity.
Keywords: CMV; COVID‐19; aging; antigen‐specific CD8+ T cells; immunosenescence.
. 2025 Mar;55(3):e202451565.
doi: 10.1002/eji.202451565. Age and Latent Cytomegalovirus Infection Do Not Affect the Magnitude of De Novo SARS-CoV-2-Specific CD8[SUP]+[/SUP] T Cell Responses
Jet van den Dijssel[SUP] 1 2 [/SUP], Veronique A L Konijn[SUP] 1 2 [/SUP], Mariël C Duurland[SUP] 1 2 [/SUP], Rivka de Jongh[SUP] 1 2 [/SUP], Lianne Koets[SUP] 1 3 [/SUP], Barbera Veldhuisen[SUP] 1 4 [/SUP], Hilde Raaphorst[SUP] 5 [/SUP], Annelies W Turksma[SUP] 5 [/SUP], Julian J Freen-van Heeren[SUP] 5 [/SUP], Maurice Steenhuis[SUP] 1 [/SUP], Theo Rispens[SUP] 1 2 6 [/SUP], C Ellen van der Schoot[SUP] 1 [/SUP], S Marieke van Ham[SUP] 1 2 7 [/SUP], Rene A W van Lier[SUP] 8 [/SUP], Klaas P J M van Gisbergen[SUP] 1 2 9 [/SUP], Anja Ten Brinke[SUP] 1 2 [/SUP], Carolien E van de Sandt[SUP] 1 2 10 [/SUP]
Affiliations
- PMID: 40071711
- DOI: 10.1002/eji.202451565
Immunosenescence, age-related immune dysregulation, reduces immunity upon vaccinations and infections. Cytomegalovirus (CMV) infection results in declining naïve (T[SUB]naïve[/SUB]) and increasing terminally differentiated (T[SUB]emra[/SUB]) 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[SUP]+[/SUP] 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[SUP]+[/SUP] T cell populations directly ex vivo. Neither age nor CMV affected SARS-CoV-2-specific CD8[SUP]+[/SUP] T cell frequencies, despite reduced total CD8[SUP]+[/SUP] T[SUB]naïve[/SUB] cells in older CMV[SUP]-[/SUP] and CMV[SUP]+[/SUP] individuals. Robust SARS-CoV-2-specific central memory CD8[SUP]+[/SUP] T (T[SUB]cm[/SUB]) 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[SUP]+[/SUP] T cell response. However, SARS-CoV-2-specific CD8[SUP]+[/SUP] T cells of older CMV[SUP]-[/SUP] individuals displayed the lowest stem cell memory (T[SUB]scm[/SUB]), highest T[SUB]emra[/SUB] and PD1[SUP]+[/SUP] populations, suggesting that age, not CMV, may impact long-term SARS-CoV-2 immunity.
Keywords: CMV; COVID‐19; aging; antigen‐specific CD8+ T cells; immunosenescence.