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Selective blockade of herpesvirus entry mediator-B and T lymphocyte attenuator pathway ameliorates acute graft-versus-host reaction

del Rio, Maria-Luisa
Jones, Nick D
Norris, Paula
Shintani, Yasushi
Ware, Carl F
Rodriguez-Barbosa, Jose-Ignacio
Published in Journal of Immunology. 2012, vol. 188, no. 10, p. 4885-96
Abstract 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.
Keywords Adoptive TransferAnimalsB-Lymphocyte Subsets/immunology/transplantationCHO CellsCell Movement/genetics/immunologyCricetinaeFemaleGraft vs Host Reaction/immunologyMiceMice, Inbred BALB CMice, Inbred C57BLRatsRats, Inbred LewReceptors, Immunologic/antagonists & inhibitors/physiologyReceptors, Tumor Necrosis Factor, Member 14/administration & dosage/antagonists & inhibitors/geneticsRecombinant Fusion Proteins/administration & dosageSignal Transduction/immunologySpleen/cytology/immunologyT-Lymphocyte Subsets/immunology/secretion/transplantation
PMID: 22490863
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Research group Cultures cellulaires et transplantations (519)
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DEL RIO, Maria-Luisa et al. Selective blockade of herpesvirus entry mediator-B and T lymphocyte attenuator pathway ameliorates acute graft-versus-host reaction. In: Journal of Immunology, 2012, vol. 188, n° 10, p. 4885-96. https://archive-ouverte.unige.ch/unige:27752

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Deposited on : 2013-05-08

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