title: CD4+T-cell engagement by both wild-type and variant HCV peptides modulates the conversion of viral clearing helper T cells to Tregs.
abstract: OBJECTIVE
  To determine whether modulation of T-cell responses by naturally occurring viral variants caused an increase in numbers of Tregs in HCV-infected patients.
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, University of Utah School of Medicine, 30 North 1900 East, 3R330 SOM, Salt Lake City, UT 84132, USA.
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Cusick
authors.affiliation: Department of Pathology, University of Utah School of Medicine, 30 North 1900 East, 3R330 SOM, Salt Lake City, UT 84132, USA.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Libbey
authors.affiliation: Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Joan
authors.initials: J
authors.lastname: Cox Gill
authors.affiliation: Department of Pathology, University of Utah School of Medicine, 30 North 1900 East, 3R330 SOM, Salt Lake City, UT 84132, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Fujinami
authors.affiliation: Department of Pathology, University of Utah School of Medicine, 30 North 1900 East, 3R330 SOM, Salt Lake City, UT 84132, USA.
authors.forename: David D
authors.initials: DD
authors.lastname: Eckels
keywords: HCV; altered peptide ligand; human PBMCs; regulatory T cells