RT journal article
T1 CD4+ primary T cells expressing HCV-core protein upregulate Foxp3 and IL-10, suppressing CD4 and CD8 T cells
A1 Fernández Ponce, Cecilia Matilde
A1 Domínguez Villar, Margarita
A1 Aguado Vidal, Enrique
A1 García Cózar, Francisco José
A2 BiomedicinaBiotecnología y Salud Pública
K1 CD4+ Primary T Cells
K1 HCV-Core Protein
K1 regulatory T cells
K1 Foxp3
AB Adaptive T cell responses are critical for controlling HCV infection. While there is clinical evidence of a relevant role for regulatory T cells in chronic HCV-infected patients, based on their increased number and function; mechanisms underlying such a phenomena are still poorly understood. Accumulating evidence suggests that proteins from Hepatitis C virus can suppress host immune responses. We and others have shown that HCV is present in CD4+ lymphocytes from chronically infected patients and that HCV-core protein induces a state of unresponsiveness in the CD4+ tumor cell line Jurkat. Here we show that CD4+ primary T cells lentivirally transduced with HCV-core, not only acquire an anergic phenotype but also inhibit IL-2 production and proliferation of bystander CD4+ or CD8+ T cells in response to anti-CD3 plus anti-CD28 stimulation. Core-transduced CD4+ T cells show a phenotype characterized by an increased basal secretion of the regulatory cytokine IL-10, a decreased IFN-c production upon stimulation, as well as expression of regulatory T cell markers, CTLA-4, and Foxp3. A significant induction of CD4+CD25+CD127lowPD-1highTIM-3high regulatory T cells with an exhausted phenotype was also observed. Moreover, CCR7 expression decreased in HCV-core expressing CD4+ T cells explaining their sequestration in inflamed tissues such as the infected liver. This work provides a new perspective on de novo generation of regulatory CD4+ T cells in the periphery, induced by the expression of a single viral protein.
PB PUBLIC LIBRARY SCIENCE
SN 1932-6203
YR 2014
FD 2014-01-20
LK http://hdl.handle.net/10498/30289
UL http://hdl.handle.net/10498/30289
LA eng
NO Ministerio de Ciencia e Innovación (España)(SAF2009-09449); Consejería de Salud, Junta de Andalucía (PI-0007/2007); Consejería de Economía, Innovacion y Ciencia, Junta de Andalucía (P08-CTS-04348))
DS Repositorio Institucional de la Universidad de Cádiz
RD 07-nov-2026