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

Research output: Contribution to journalArticlepeer-review

Authors

  • Maria-Luisa del Rio
  • Leo Buhler
  • Paula Norris
  • Yasushi Shintani
  • Carl F Ware
  • Jose-Ignacio Rodriguez-Barbosa

Colleges, School and Institutes

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.

Details

Original languageEnglish
Pages (from-to)4885-96
Number of pages12
JournalJournal of Immunology
Volume188
Issue number10
Early online date6 Apr 2012
Publication statusPublished - 15 May 2012

Keywords

  • Cell Movement, Animals, Rats, Inbred Lew, B-Lymphocyte Subsets, Spleen, Recombinant Fusion Proteins, Mice, Receptors, Tumor Necrosis Factor, Member 14, Mice, Inbred BALB C, Rats, Adoptive Transfer, Receptors, Immunologic, Mice, Inbred C57BL, CHO Cells, Signal Transduction, Female, T-Lymphocyte Subsets, Cricetinae, Graft vs Host Reaction