Publicações científicas

In vitro and in vivo down-regulation of regulatory T cell activity with a peptide inhibitor of TGF-beta1

Gil-Guerrero L, Dotor J, Huibregtse IL, Casares N, López-Vázquez AB, Rudilla F, Riezu-Boj JI, López-Sagaseta J, Hermida J, Van Deventer S, Bezunartea J, Llopiz D, Sarobe P, Prieto J, Borrás-Cuesta F, Lasarte JJ.
Center for Applied Medical Research, Division of Hepatology and Gene Therapy, University of Navarra, Pamplona, Spain

Revisão:Journal of Immunology

Data: 1/Jul/2008

Hepatologia

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.

CITAÇÃO DO ARTIGO J Immunol. 2008 Jul 1;181(1):126-35

talvezlhe interesse

QUE TECNOLOGIA UTILIZAMOS? 

A Clínica é o hospital privado com maiores recursos tecnológicos de Espanha, tudo num único centro.

Imagen de un PET, tecnología de vanguardia en la Clínica Universidad de Navarra

OS NOSSOS
PROFISSIONAIS

Os profissionais da Clínica realizam um trabalho contínuo de investigação e formação, sempre em benefício do paciente.

Imagen profesionales de la Clínica Universidad de Navarra

RAZÕES PARA VIR
À CLÍNICA

Conheça porque é que somos diferentes em relação a outros centros sanitários. Qualidade, rapidez, comodidade e resultados.

Imagen del edificio de la Clínica Universidad de Navarra