Functional SARS-CoV-2 cross-reactive CD4+ T cells established in early childhood decline with age
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+ 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+ T cell responses targeting spike, nucleocapsid, and membrane were closely linked to the frequency of OC43-specific memory CD4+ T cells in childhood. The functional quality of the cross-reactive memory CD4+ 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+ 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:120 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 120(2023), 12 vom: 21. März, Seite e2220320120 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Humbert, Marion [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.03.2023 Date Revised 08.04.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1073/pnas.2220320120 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM354232339 |
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| 245 | 1 | 0 | |a Functional SARS-CoV-2 cross-reactive CD4+ T cells established in early childhood decline with age |
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| 500 | |a Date Revised 08.04.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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+ 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+ T cell responses targeting spike, nucleocapsid, and membrane were closely linked to the frequency of OC43-specific memory CD4+ T cells in childhood. The functional quality of the cross-reactive memory CD4+ 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+ 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a T cell specificity | |
| 650 | 4 | |a age groups | |
| 650 | 4 | |a cross-protection | |
| 650 | 4 | |a human coronavirus OC43 | |
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| 700 | 1 | |a Olofsson, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Wullimann, David |e verfasserin |4 aut | |
| 700 | 1 | |a Niessl, Julia |e verfasserin |4 aut | |
| 700 | 1 | |a Hodcroft, Emma B |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Curtis |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Sohlberg, Ebba |e verfasserin |4 aut | |
| 700 | 1 | |a Dyrdak, Robert |e verfasserin |4 aut | |
| 700 | 1 | |a Mikaeloff, Flora |e verfasserin |4 aut | |
| 700 | 1 | |a Neogi, Ujjwal |e verfasserin |4 aut | |
| 700 | 1 | |a Albert, Jan |e verfasserin |4 aut | |
| 700 | 1 | |a Malmberg, Karl-Johan |e verfasserin |4 aut | |
| 700 | 1 | |a Lund-Johansen, Fridtjof |e verfasserin |4 aut | |
| 700 | 1 | |a Aleman, Soo |e verfasserin |4 aut | |
| 700 | 1 | |a Björkhem-Bergman, Linda |e verfasserin |4 aut | |
| 700 | 1 | |a Jenmalm, Maria C |e verfasserin |4 aut | |
| 700 | 1 | |a Ljunggren, Hans-Gustaf |e verfasserin |4 aut | |
| 700 | 1 | |a Buggert, Marcus |e verfasserin |4 aut | |
| 700 | 1 | |a Karlsson, Annika C |e verfasserin |4 aut | |
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