Primary EBV Infection Induces an Acute Wave of Activated Antigen-Specific Cytotoxic CD4+ T Cells
Copyright © 2019 The Authors..
CD4+ T cells are essential for immune protection against viruses, yet their multiple roles remain ill-defined at the single-cell level in humans. Using HLA class II tetramers, we studied the functional properties and clonotypic architecture of EBV-specific CD4+ T cells in patients with infectious mononucleosis, a symptomatic manifestation of primary EBV infection, and in long-term healthy carriers of EBV. We found that primary infection elicited oligoclonal expansions of TH1-like EBV-specific CD4+ T cells armed with cytotoxic proteins that responded immediately ex vivo to challenge with EBV-infected B cells. Importantly, these acutely generated cytotoxic CD4+ T cells were highly activated and transcriptionally distinct from classically described cytotoxic CD4+ memory T cells that accumulate during other persistent viral infections, including CMV and HIV. In contrast, EBV-specific memory CD4+ T cells displayed increased cytokine polyfunctionality but lacked cytotoxic activity. These findings suggested an important effector role for acutely generated cytotoxic CD4+ T cells that could potentially be harnessed to improve the efficacy of vaccines against EBV.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:203 |
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| Enthalten in: |
Journal of immunology (Baltimore, Md. : 1950) - 203(2019), 5 vom: 01. Sept., Seite 1276-1287 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Meckiff, Benjamin J [VerfasserIn] |
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| Anmerkungen: |
Date Completed 06.04.2020 Date Revised 10.01.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.4049/jimmunol.1900377 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM299210391 |
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| 245 | 1 | 0 | |a Primary EBV Infection Induces an Acute Wave of Activated Antigen-Specific Cytotoxic CD4+ T Cells |
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| 500 | |a Date Completed 06.04.2020 | ||
| 500 | |a Date Revised 10.01.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2019 The Authors. | ||
| 520 | |a CD4+ T cells are essential for immune protection against viruses, yet their multiple roles remain ill-defined at the single-cell level in humans. Using HLA class II tetramers, we studied the functional properties and clonotypic architecture of EBV-specific CD4+ T cells in patients with infectious mononucleosis, a symptomatic manifestation of primary EBV infection, and in long-term healthy carriers of EBV. We found that primary infection elicited oligoclonal expansions of TH1-like EBV-specific CD4+ T cells armed with cytotoxic proteins that responded immediately ex vivo to challenge with EBV-infected B cells. Importantly, these acutely generated cytotoxic CD4+ T cells were highly activated and transcriptionally distinct from classically described cytotoxic CD4+ memory T cells that accumulate during other persistent viral infections, including CMV and HIV. In contrast, EBV-specific memory CD4+ T cells displayed increased cytokine polyfunctionality but lacked cytotoxic activity. These findings suggested an important effector role for acutely generated cytotoxic CD4+ T cells that could potentially be harnessed to improve the efficacy of vaccines against EBV | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a CD4 Antigens |2 NLM | |
| 700 | 1 | |a Ladell, Kristin |e verfasserin |4 aut | |
| 700 | 1 | |a McLaren, James E |e verfasserin |4 aut | |
| 700 | 1 | |a Ryan, Gordon B |e verfasserin |4 aut | |
| 700 | 1 | |a Leese, Alison M |e verfasserin |4 aut | |
| 700 | 1 | |a James, Eddie A |e verfasserin |4 aut | |
| 700 | 1 | |a Price, David A |e verfasserin |4 aut | |
| 700 | 1 | |a Long, Heather M |e verfasserin |4 aut | |
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| 912 | |a GBV_NLM | ||
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