1. Primary EBV Infection Induces an Acute Wave of Activated Antigen-Specific Cytotoxic CD4 + T Cells.
- Author
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Meckiff BJ, Ladell K, McLaren JE, Ryan GB, Leese AM, James EA, Price DA, and Long HM
- Subjects
- B-Lymphocytes immunology, CD4 Antigens immunology, Humans, Immunologic Memory immunology, Infectious Mononucleosis immunology, CD4-Positive T-Lymphocytes immunology, Cytotoxicity, Immunologic immunology, Epstein-Barr Virus Infections immunology, Herpesvirus 4, Human immunology, T-Lymphocytes, Cytotoxic immunology
- Abstract
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 TH 1-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., (Copyright © 2019 The Authors.)- Published
- 2019
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