tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2023 Mar 21;120(12):e2220320120.
doi: 10.1073/pnas.2220320120. Epub 2023 Mar 14.
Functional SARS-CoV-2 cross-reactive CD4[SUP]+[/SUP] T cells established in early childhood decline with age
Marion Humbert[SUP] 1 2 [/SUP], Anna Olofsson[SUP] 1 [/SUP], David Wullimann[SUP] 2 [/SUP], Julia Niessl[SUP] 2 [/SUP], Emma B Hodcroft[SUP] 3 4 [/SUP], Curtis Cai[SUP] 2 [/SUP], Yu Gao[SUP] 2 [/SUP], Ebba Sohlberg[SUP] 2 [/SUP], Robert Dyrdak[SUP] 5 6 [/SUP], Flora Mikaeloff[SUP] 1 [/SUP], Ujjwal Neogi[SUP] 1 [/SUP], Jan Albert[SUP] 5 6 [/SUP], Karl-Johan Malmberg[SUP] 2 7 8 [/SUP], Fridtjof Lund-Johansen[SUP] 9 10 [/SUP], Soo Aleman[SUP] 11 12 [/SUP], Linda Björkhem-Bergman[SUP] 13 14 [/SUP], Maria C Jenmalm[SUP] 15 [/SUP], Hans-Gustaf Ljunggren[SUP] 2 [/SUP], Marcus Buggert[SUP] 2 [/SUP], Annika C Karlsson[SUP] 1 [/SUP]
Affiliations
Abstract
Pre-existing SARS-CoV-2-reactive T cells have been identified in SARS-CoV-2-unexposed individuals, potentially modulating COVID-19 and vaccination outcomes. Here, we provide evidence that functional cross-reactive memory CD4[SUP]+[/SUP] T cell immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is established in early childhood, mirroring early seroconversion with seasonal human coronavirus OC43. Humoral and cellular immune responses against OC43 and SARS-CoV-2 were assessed in SARS-CoV-2-unexposed children (paired samples at age two and six) and adults (age 26 to 83). Pre-existing SARS-CoV-2-reactive CD4[SUP]+[/SUP] T cell responses targeting spike, nucleocapsid, and membrane were closely linked to the frequency of OC43-specific memory CD4[SUP]+[/SUP] T cells in childhood. The functional quality of the cross-reactive memory CD4[SUP]+[/SUP] T cell responses targeting SARS-CoV-2 spike, but not nucleocapsid, paralleled OC43-specific T cell responses. OC43-specific antibodies were prevalent already at age two. However, they did not increase further with age, contrasting with the antibody magnitudes against HKU1 (β-coronavirus), 229E and NL63 (α-coronaviruses), rhinovirus, Epstein-Barr virus (EBV), and influenza virus, which increased after age two. The quality of the memory CD4[SUP]+[/SUP] T cell responses peaked at age six and subsequently declined with age, with diminished expression of interferon (IFN)-γ, interleukin (IL)-2, tumor necrosis factor (TNF), and CD38 in late adulthood. Age-dependent qualitative differences in the pre-existing SARS-CoV-2-reactive T cell responses may reflect the ability of the host to control coronavirus infections and respond to vaccination.
Keywords: SARS-CoV-2; T cell specificity; age groups; cross-protection; human coronavirus OC43.
. 2023 Mar 21;120(12):e2220320120.
doi: 10.1073/pnas.2220320120. Epub 2023 Mar 14.
Functional SARS-CoV-2 cross-reactive CD4[SUP]+[/SUP] T cells established in early childhood decline with age
Marion Humbert[SUP] 1 2 [/SUP], Anna Olofsson[SUP] 1 [/SUP], David Wullimann[SUP] 2 [/SUP], Julia Niessl[SUP] 2 [/SUP], Emma B Hodcroft[SUP] 3 4 [/SUP], Curtis Cai[SUP] 2 [/SUP], Yu Gao[SUP] 2 [/SUP], Ebba Sohlberg[SUP] 2 [/SUP], Robert Dyrdak[SUP] 5 6 [/SUP], Flora Mikaeloff[SUP] 1 [/SUP], Ujjwal Neogi[SUP] 1 [/SUP], Jan Albert[SUP] 5 6 [/SUP], Karl-Johan Malmberg[SUP] 2 7 8 [/SUP], Fridtjof Lund-Johansen[SUP] 9 10 [/SUP], Soo Aleman[SUP] 11 12 [/SUP], Linda Björkhem-Bergman[SUP] 13 14 [/SUP], Maria C Jenmalm[SUP] 15 [/SUP], Hans-Gustaf Ljunggren[SUP] 2 [/SUP], Marcus Buggert[SUP] 2 [/SUP], Annika C Karlsson[SUP] 1 [/SUP]
Affiliations
- PMID: 36917669
- DOI: 10.1073/pnas.2220320120
Abstract
Pre-existing SARS-CoV-2-reactive T cells have been identified in SARS-CoV-2-unexposed individuals, potentially modulating COVID-19 and vaccination outcomes. Here, we provide evidence that functional cross-reactive memory CD4[SUP]+[/SUP] T cell immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is established in early childhood, mirroring early seroconversion with seasonal human coronavirus OC43. Humoral and cellular immune responses against OC43 and SARS-CoV-2 were assessed in SARS-CoV-2-unexposed children (paired samples at age two and six) and adults (age 26 to 83). Pre-existing SARS-CoV-2-reactive CD4[SUP]+[/SUP] T cell responses targeting spike, nucleocapsid, and membrane were closely linked to the frequency of OC43-specific memory CD4[SUP]+[/SUP] T cells in childhood. The functional quality of the cross-reactive memory CD4[SUP]+[/SUP] T cell responses targeting SARS-CoV-2 spike, but not nucleocapsid, paralleled OC43-specific T cell responses. OC43-specific antibodies were prevalent already at age two. However, they did not increase further with age, contrasting with the antibody magnitudes against HKU1 (β-coronavirus), 229E and NL63 (α-coronaviruses), rhinovirus, Epstein-Barr virus (EBV), and influenza virus, which increased after age two. The quality of the memory CD4[SUP]+[/SUP] T cell responses peaked at age six and subsequently declined with age, with diminished expression of interferon (IFN)-γ, interleukin (IL)-2, tumor necrosis factor (TNF), and CD38 in late adulthood. Age-dependent qualitative differences in the pre-existing SARS-CoV-2-reactive T cell responses may reflect the ability of the host to control coronavirus infections and respond to vaccination.
Keywords: SARS-CoV-2; T cell specificity; age groups; cross-protection; human coronavirus OC43.