Therapeutic Blockade of LIGHT Interaction With Herpesvirus Entry Mediator and Lymphotoxin β Receptor Attenuates In Vivo Cytotoxic Allogeneic Responses.

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Serval ID
serval:BIB_355F76D51F83
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Therapeutic Blockade of LIGHT Interaction With Herpesvirus Entry Mediator and Lymphotoxin β Receptor Attenuates In Vivo Cytotoxic Allogeneic Responses.
Journal
Transplantation
Author(s)
Del Rio M.L., Fernandez-Renedo C., Scheu S., Pfeffer K., Shintani Y., Kronenberg M., Chaloin O., Schneider P., Rodriguez-Barbosa J.I.
ISSN
1534-6080 (Electronic)
ISSN-L
0041-1337
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
98
Number
11
Pages
1165-1174
Language
english
Abstract
BACKGROUND: Tumor necrosis factor/tumor necrosis factor receptor superfamily members conform a group of molecular interaction pathways of essential relevance during the process of T-cell activation and differentiation toward effector cells and particularly for the maintenance phase of the immune response. Specific blockade of these interacting pathways, such as CD40-CD40L, contributes to modulate the deleterious outcome of allogeneic immune responses. We postulated that antagonizing the interaction of LIGHT expression on activated T cells with its receptors, herpesvirus entry mediator and lymphotoxin β receptor, may decrease T cell-mediated allogeneic responses.
METHODS: A flow cytometry competition assay was designed to identify anti-LIGHT monoclonal antibodies capable to prevent the interaction of mouse LIGHT with its receptors expressed on transfected cells. An antibody with the desired specificity was evaluated in a short-term in vivo allogeneic cytotoxic assay and tested for its ability to detect endogenous mouse LIGHT.
RESULTS: We provide evidence for the first time that in mice, as previously described in humans, LIGHT protein is rapidly and transiently expressed after T-cell activation, and this expression was stronger on CD8 T cells than on CD4 T cells. Two anti-LIGHT antibodies prevented interactions of mouse LIGHT with its two known receptors, herpesvirus entry mediator and lymphotoxin β receptor. In vivo administration of anti-LIGHT antibody (clone 10F12) ameliorated host antidonor short-term cytotoxic response in wild type B6 mice, although to a lesser extent than that observed in LIGHT-deficient mice.
CONCLUSION: The therapeutic targeting of LIGHT may contribute to achieve a better control of cytotoxic responses refractory to current immunosuppressive drugs in transplantation.
Keywords
HVEM (TNFRSF14), LIGHT (TNFSF14), LT beta R (TNFRSF3), DcR3 (TNFRSF6b), Costimulation, Transplantation, Alloreactivity, Graft rejection, Graft versus host disease, Cytotoxicity
Pubmed
Web of science
Create date
15/12/2014 18:06
Last modification date
20/08/2019 13:22
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