Article Title: Immunotherapeutic targeting of LIGHT/LTβR/HVEM pathway fully recapitulates the reduced cytotoxic phenotype of LIGHT-deficient T cells
Author(s): Maria-Luisa del Rio, Carlos Fernandez-Renedo, Olivier Chaloin, Stefanie Scheu, Klaus Pfeffer, Yasushi Shintani, Jose-Antonio Perez-Simon, Pascal Schneider, and Jose-Ignacio Rodriguez-Barbosa
Journal: mAbs
Bibliometrics: Published in Volume 8, Issue 3, pp. 478–490
DOI: 10.1080/19420862.2015.1132130
Publisher: Taylor & Francis
In the abstract and keywords for the article listed above, the incorrect abbreviations were supplied for two receptors. The official abbreviation of the herpes virus entry mediator was given as TNFSFR14 but should have been provided as TNFRSF14, and the official abbreviation of the lymphotoxin β receptor was given as TNFSFR3 but should have been provided as TNFRSF3. An abstract with the correct abbreviations is printed below. The authors apologize of the error.
ABSTRACT
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, TNFRSF14) and the lymphotoxin β receptor (LTβR, TNFRSF3). 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.