Primary EBV Infection Induces an Acute Wave of Activated Antigen-Specific Cytotoxic CD4+ T Cells.
J Immunol
; 203(5): 1276-1287, 2019 09 01.
Article
in En
| MEDLINE
| ID: mdl-31308093
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 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.
Full text:
1
Database:
MEDLINE
Main subject:
T-Lymphocytes, Cytotoxic
/
CD4-Positive T-Lymphocytes
/
Herpesvirus 4, Human
/
Epstein-Barr Virus Infections
/
Cytotoxicity, Immunologic
Limits:
Humans
Language:
En
Journal:
J Immunol
Year:
2019
Type:
Article
Affiliation country:
United kingdom