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Therapeutic blockade of LIGHT interaction with herpesvirus entry mediator and lymphotoxin β receptor attenuates in vivo cytotoxic allogeneic responses.

Authors :
del Rio ML
Fernandez-Renedo C
Scheu S
Pfeffer K
Shintani Y
Kronenberg M
Chaloin O
Schneider P
Rodriguez-Barbosa JI
Source :
Transplantation [Transplantation] 2014 Dec 15; Vol. 98 (11), pp. 1165-74.
Publication Year :
2014

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.<br />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.<br />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.<br />Conclusion: The therapeutic targeting of LIGHT may contribute to achieve a better control of cytotoxic responses refractory to current immunosuppressive drugs in transplantation.

Details

Language :
English
ISSN :
1534-6080
Volume :
98
Issue :
11
Database :
MEDLINE
Journal :
Transplantation
Publication Type :
Academic Journal
Accession number :
25226173
Full Text :
https://doi.org/10.1097/TP.0000000000000417