Matthew F Cusick1, Jane E Libbey1, Joan Cox Gill2, Robert S Fujinami1, David D Eckels1. 1. Department of Pathology, University of Utah School of Medicine, 30 North 1900 East, 3R330 SOM, Salt Lake City, UT 84132, USA. 2. Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI 53226, USA.
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.
AIM: To determine whether modulation of T-cell responses by naturally occurring viral variants caused an increase in numbers of Tregs in HCV-infectedpatients. 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.
Entities:
Keywords:
HCV; altered peptide ligand; human PBMCs; regulatory T cells
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