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Título
Immunotherapeutic targeting of LIGHT/LTβR/HVEM pathway fully recapitulates the reduced cytotoxic phenotype of LIGHT-deficient T cells
Autor
Facultad/Centro
Área de conocimiento
Título de la revista
mAbs
Número de la revista
3
Cita Bibliográfica
del Rio, M. L., Fernández Renedo, C., Chaloin, O., Scheu, S., Pfeffer, K., Shintani, Y., Pérez Simón, J.-A., Schneider, P., & Rodríguez Barbosa, J.-I. (2016). Immunotherapeutic targeting of LIGHT/LTβR/HVEM pathway fully recapitulates the reduced cytotoxic phenotype of LIGHT-deficient T cells. mAbs, 8(3), 478-490. https://doi.org/10.1080/19420862.2015.1132130
Editorial
Taylor and Francis Group
Fecha
2016
ISSN
1942-0862
Resumen
[EN] Tumor necrosis factor (TNF)/TNF receptor (TNFR) superfamily members play essential roles in the development of the different phases of the immune response. Mouse LIGHT (TNFSF14) is a type II transmembrane protein with a C-terminus extracellular TNF homology domain (THD) that assembles in homotrimers and regulates the course of the immune responses by signaling through 2 receptors, the herpes virus entry mediator (HVEM, TNFSFR14) and the lymphotoxin β receptor (LTβR, TNFSFR3). LIGHT is a membrane-bound protein transiently expressed on activated T cells, natural killer (NK) cells and immature dendritic cells that can be proteolytically cleaved by a metalloprotease and released to the extracellular milieu. The immunotherapeutic potential of LIGHT blockade was evaluated in vivo. Administration of an antagonist of LIGHT interaction with its receptors attenuated the course of graft-versus-host reaction and recapitulated the reduced cytotoxic activity of LIGHT-deficient T cells adoptively transferred into non-irradiated semiallogeneic recipients. The lack of LIGHT expression on donor T cells or blockade of LIGHT interaction with its receptors slowed down the rate of T cell proliferation and decreased the frequency of precursor alloreactive T cells, retarding T cell differentiation toward effector T cells. The blockade of LIGHT/LTβR/HVEM pathway was associated with delayed downregulation of interleukin-7Rα and delayed upregulation of inducible costimulatory molecule expression on donor alloreactive CD8 T cells that are typical features of impaired T cell differentiation. These results expose the relevance of LIGHT/LTβR/HVEM interaction for the potential therapeutic control of the allogeneic immune responses mediated by alloreactive CD8 T cells that can contribute to prolong allograft survival.
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Palabras clave
Peer review
SI
ID proyecto
- info:eu-repo/grantAgreement/MINECO/Programa Estatal de I+D+I Orientada a los Retos de la Sociedad/PI13/00029 /ES/ Estudio de la interacción CD160/HVEM como diana para el control del rechazo mediado por linfocitos T CD8 y células NK en un biomodelo preclínico de aloreactividad//
- info:eu-repo/grantAgreement/Junta de Castilla y León/ / LE093U13/ES/ ESTUDIO DE LAS INTERACCIONES DE CD160 CON SU RECEPTOR HVEM EN UN MODELO PRECLÍNICO DE ALOREACTIVIDAD QUE MIMETIZA LA ENFERMEDAD DE INJERTO FRENTE A HUÉSPED EN TRASPLANTE//
- info:eu-repo/grantAgreement/MINECO/Acción Estratégica de Salud/CP12/03063/ES/CP12/03063/ /
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