Gil-Guerrero, L. (Lucía)

Filtering

2006 - 20083

Settings

Author search.filters.isAuthorOfPublication.a6d65e9b-a437-4492-a35e-7a7ec8feace8

Search Results

Now showing 1 - 3 of 3
  • Thumbnail Image
    New therapies for hepatitis C
    (Elsevier, 2006) Gil-Guerrero, L. (Lucía); Prieto, J. (Jesús); Sarobe, P. (Pablo)
    Hepatitis C virus is an important public health threat, not only because of the high prevalence of this infection in western and third world countries, but also because of the high rate of resistance to the available antiviral therapy that consists on the use of pegylated interferon plus ribavirin. Currently, new forms of therapy are being developed based on a more precise knowledge of the structure and function of the viral proteins and of the strategies used by the virus to escape the immune and interferon systems. The new therapeutic approaches aim at different objectives: a) the inhibition of viral replication by blocking the viral protease and/or replicase; b) the use of other types of interferon with more potent antiviral effect, c) the induction of a specific anti-viral immune response by means of immunomodulatory compounds or therapeutic vaccination, d) the blockade of "de novo" infection of other cells with neutralizing antibodies, e) the induction of a antiviral state in the liver by transferring to this organ the gene of interferon and/or immunostimulating cytokines.
  • Thumbnail Image
    Upregulation of indoleamine 2,3-dioxygenase in hepatitis C virus infection
    (American Society for Microbiology, 2007) Civeira, M.P. (María Pilar); Riezu-Boj, J.I. (José Ignacio); Gil-Guerrero, L. (Lucía); Larrea, E. (Esther); Rollier, C.S. (Christine S.); Aldabe, R. (Rafael); Casares, N. (Noelia); Verstrepen, B.E. (Babs E.); Sarobe, P. (Pablo); Heeney, J.L. (Jonathan L.)
    Indoleamine 2,3-dioxygenase (IDO) is induced by proinflammatory cytokines and by CTLA-4-expressing T cells and constitutes an important mediator of peripheral immune tolerance. In chronic hepatitis C, we found upregulation of IDO expression in the liver and an increased serum kynurenine/tryptophan ratio (a reflection of IDO activity). Huh7 cells supporting hepatitis C virus (HCV) replication expressed higher levels of IDO mRNA than noninfected cells when stimulated with gamma interferon or when cocultured with activated T cells. In infected chimpanzees, hepatic IDO expression decreased in animals that cured the infection, while it remained high in those that progressed to chronicity. For both patients and chimpanzees, hepatic expression of IDO and CTLA-4 correlated directly. Induction of IDO may dampen T-cell reactivity to viral antigens in chronic HCV infection
  • Thumbnail Image
    In vitro and in vivo down-regulation of regulatory T cell activity with a peptide inhibitor of TGF-beta1
    (American association of immunologists, 2008) Riezu-Boj, J.I. (José Ignacio); Gil-Guerrero, L. (Lucía); Dotor, J. (Javier); Deventer, S. (Sander) van; Huibregtse, I.L. (Inge Louise); Borras-Cuesta, F. (Francisco); Hermida, J. (José); Rudilla, F. (Francesc); Casares, N. (Noelia); Prieto, J. (Jesús); Lopez-Vazquez, A.B. (Ana B.); Bezunartea, J. (Jaione); Llopiz, D. (Diana); Sarobe, P. (Pablo); Lopez-Sagaseta, J. (Jacinto); Lasarte, J.J. (Juan José)
    Down-regulation of CD4+CD25+ regulatory T (Treg) cell function might be beneficial to enhance the immunogenicity of viral and tumor vaccines or to induce breakdown of immunotolerance. Although the mechanism of suppression used by Treg cells remains controversial, it has been postulated that TGF-beta1 mediates their immunosuppressive activity. In this study, we show that P17, a short synthetic peptide that inhibits TGF-beta1 and TGF-beta2 developed in our laboratory, is able to inhibit Treg activity in vitro and in vivo. In vitro studies demonstrate that P17 inhibits murine and human Treg-induced unresponsiveness of effector T cells to anti-CD3 stimulation, in an MLR or to a specific Ag. Moreover, administration of P17 to mice immunized with peptide vaccines containing tumor or viral Ags enhanced anti-vaccine immune responses and improved protective immunogenicity against tumor growth or viral infection or replication. When CD4+ T cells purified from OT-II transgenic mice were transferred into C57BL/6 mice bearing s.c. EG.7-OVA tumors, administration of P17 improved their proliferation, reduced the number of CD4+Foxp3+ T cells, and inhibited tumor growth. Also, P17 prevented development of immunotolerance induced by oral administration of OVA by genetically modified Lactococcus lactis in DO11.10 transgenic mice sensitized by s.c. injection of OVA. These findings demonstrate that peptide inhibitors of TGF-beta may be a valuable tool to enhance vaccination efficacy and to break tolerance against pathogens or tumor Ags.