Immunotherapeutic targeting of LIGHT/LTβR/HVEM pathway fully recapitulates the reduced cytotoxic phenotype of LIGHT-deficient T cells.

Détails

Ressource 1Télécharger: DelRio2016.pdf (2168.89 [Ko])
Etat: Public
Version: Author's accepted manuscript
ID Serval
serval:BIB_E05D044E35D3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Immunotherapeutic targeting of LIGHT/LTβR/HVEM pathway fully recapitulates the reduced cytotoxic phenotype of LIGHT-deficient T cells.
Périodique
mAbs
Auteur(s)
Del Rio M.L., Fernandez-Renedo C., Chaloin O., Scheu S., Pfeffer K., Shintani Y., Perez-Simon J.A., Schneider P., Rodriguez-Barbosa J.I.
ISSN
1942-0870 (Electronic)
ISSN-L
1942-0862
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
8
Numéro
3
Pages
478-490
Langue
anglais
Notes
Publication types: Journal Article Publication Status: ppublish
Résumé
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.
Pubmed
Web of science
Open Access
Oui
Création de la notice
01/05/2016 17:32
Dernière modification de la notice
20/08/2019 17:04
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