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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Inmunología hepatitis virales > DA - CIMA - Terapia génica y Hepatología - Inmunología hepatitis virales - Artículos de revista >

In vitro and in vivo down-regulation of regulatory T cell activity with a peptide inhibitor of TGF-beta1
Authors: Gil-Guerrero, L. (Lucía)
Dotor, J. (Javier)
Huibregtse, I.L. (Inge Louise)
Casares, N. (Noelia)
Lopez-Vazquez, A.B. (Ana B.)
Rudilla, F. (Francesc)
Riezu-Boj, J.I. (José Ignacio)
Lopez-Sagaseta, J. (Jacinto)
Hermida, J. (José)
Deventer, S. (Sander) van
Bezunartea, J. (Jaione)
Llopiz, D. (Diana)
Sarobe, P. (Pablo)
Prieto, J. (Jesús)
Borras-Cuesta, F. (Francisco)
Lasarte, J.J. (Juan José)
Keywords: Down-Regulation/immunology
Lymphocyte Activation/immunology
Peptides/pharmacology
T-Lymphocytes, Regulatory/drug effects
Transforming Growth Factor beta1/antagonists & inhibitors
Issue Date: 2008
Publisher: American association of immunologists
Publisher version: http://www.jimmunol.org/content/181/1/126.long
ISSN: 0022-1767
Citation: Gil-Guerrero L, Dotor J, Huibregtse IL, Casares N, Lopez-Vazquez AB, Rudilla F, et al. In vitro and in vivo down-regulation of regulatory T cell activity with a peptide inhibitor of TGF-beta1. J Immunol 2008 Jul 1;181(1):126-135.
Abstract
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.
Permanent link: http://hdl.handle.net/10171/20429
Appears in Collections:DA - CUN - Medicina interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Virología - Artículos de revista
DA - CIMA - Cardiovasculares - Trombosis y Hemostasia - Artículos de Revista
DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología experimental - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología hepatitis virales - Artículos de revista

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