CD4+ T-cell engagement by both wild-type and variant HCV peptides modulates the conversion of viral clearing helper T cells to Tregs

Matthew F. Cusick*, Jane E. Libbey, Joan Cox Gill, Robert S. Fujinami, David D. Eckels

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Aim: To determine whether modulation of T-cell responses by naturally occurring viral variants caused an increase in numbers of Tregs in HCV-infected patients. Patients, materials & methods: Human peripheral blood mononuclear cells, having proliferative responses to a wild-type HCV-specific CD4 + T-cell epitope, were used to quantify, via proliferative assays, flow cytometry and class II tetramers, the effects of naturally occurring viral variants arising in the immunodominant epitope. Results: In combination, the wild-type and variant peptides led to enhanced suppression of an anti-HCV T-cell response. The variant had a lower avidity for the wild-type-specific CD4 + T cell. Variant-stimulated CD4+ T cells had increased Foxp3, compared with wild-type-stimulated cells. Conclusion: A stable viral variant from a chronic HCV subject was able to induce Tregs in multiple individuals that responded to the wild-type HCV-specific CD4+ T-cell epitope.

Original languageEnglish (US)
Pages (from-to)695-705
Number of pages11
JournalFuture Virology
Volume8
Issue number7
DOIs
StatePublished - Jul 1 2013

Keywords

  • HCV
  • altered peptide ligand
  • human PBMCs
  • regulatory T cells

ASJC Scopus subject areas

  • Virology

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