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Primary EBV infection induces an acute wave of activated antigen-specific cytotoxic CD4+ T cells

Meckiff, Benjamin J., Ladell, Kristin ORCID:, McLaren, James E. ORCID:, Ryan, Gordon B., Leese, Alison M., James, Eddie A., Price, David A. and Long, Heather M. 2019. Primary EBV infection induces an acute wave of activated antigen-specific cytotoxic CD4+ T cells. Journal of Immunology 203 (3) , ji1900377. 10.4049/jimmunol.1900377

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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 CMVand 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: American Association of Immunologists
ISSN: 0022-1767
Date of First Compliant Deposit: 25 July 2019
Date of Acceptance: 20 June 2019
Last Modified: 05 May 2023 02:49

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