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

Meckiff, Benjamin J., Ladell, Kristin, McLaren, James E., 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: 29 Aug 2019 14:09

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