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

Research output: Contribution to journalArticlepeer-review


  • Kristin Ladell
  • James McLaren
  • Alison Leese
  • Eddie James
  • David Price

External organisations

  • Cardiff University
  • Benaroya Research Institute at Virginia Mason


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.


Original languageEnglish
Pages (from-to)1276-1287
JournalJournal of Immunology
Issue number5
Early online date19 Aug 2019
Publication statusPublished - 1 Sep 2019

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