Selective Blockade of Herpesvirus Entry Mediator–B and T Lymphocyte Attenuator Pathway Ameliorates Acute Graft-versus-Host Reaction
[EN] The cosignaling network mediated by the herpesvirus entry mediator (HVEM; TNFRSF14) functions as a dual directional system that involves proinflammatory ligand, lymphotoxin that exhibits inducible expression and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes (L...
| Autores: | , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2012 |
| País: | España |
| Institución: | Ajuntament de Barcelona |
| Repositorio: | BULERIA. Repositorio Institucional de la Universidad de León |
| OAI Identifier: | oai:buleria.unileon.es:10612/24256 |
| Acceso en línea: | https://journals.aai.org/jimmunol/article/188/10/4885/85565/Selective-Blockade-of-Herpesvirus-Entry-Mediator-B https://hdl.handle.net/10612/24256 |
| Access Level: | acceso abierto |
| Palabra clave: | Inmunología Veterinaria HVEM TNFRSF14 3109 Ciencias Veterinarias 3109.03 Inmunología |
| Sumario: | [EN] The cosignaling network mediated by the herpesvirus entry mediator (HVEM; TNFRSF14) functions as a dual directional system that involves proinflammatory ligand, lymphotoxin that exhibits inducible expression and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes (LIGHT; TNFSF14), and the inhibitory Ig family member B and T lymphocyte attenuator (BTLA). To dissect the differential contributions of HVEM/BTLA and HVEM/LIGHT interactions, topographically-specific, competitive, and nonblocking anti-HVEM Abs that inhibit BTLA binding, but not LIGHT, were developed. We demonstrate that a BTLA-specific competitor attenuated the course of acute graft-versus-host reaction in a murine F 1 transfer semiallogeneic model. Selective HVEM/BTLA blockade did not inhibit donor T cell infiltration into graft-versus-host reaction target organs, but decreased the functional activity of the alloreactive T cells. These results highlight the critical role of HVEM/BTLA pathway in the control of the allogeneic immune response and identify a new therapeutic target for transplantation and autoimmune diseases |
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