{"doi":"10.4049/jimmunol.186.supp.169.48","title":"BTLA-HVEM interaction delivers bidirectional signals and modulates the severity of GVHD (169.48)","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>B and T lymphocyte attenuator (BTLA), upon interaction with herpesvirus entry mediator (HVEM), delivers an inhibitory co-signal which regulates immune response in various diseases. In graft-versus-host disease (GVHD), unexpectedly, BTLA mediates positive effects on donor T cell survival, but immunological mechanisms of this function have yet to be fully explored. Our recent studies addressed a role of BTLA in GVHD by employing the newly established agonistic anti-BTLA mAb that stimulates BTLA signal without antagonizing BTLA-HVEM interaction. We revealed that BTLA signal inhibited donor anti-host T cell responses and ameliorated GVHD with a successful engraftment of donor hematopoietic cells. These effects were dependent on BTLA signal into donor T cells but neither donor non-T cells nor recipient cells. On the other hand, expression of BTLA mutant lacking an intracellular signaling domain restored impaired survival of BTLA-deficient T cells, suggesting that BTLA also serves as a ligand and delivers HVEM prosurvival co-signal in donor T cells. Thus, BTLA-HVEM interaction delivers positive and negative bidirectional co-signals to donor T cells via HVEM and BTLA, respectively, and modulates the severity of GVHD. Additional data obtained by recent studies will be also presented.</jats:p>","journal":"The Journal of Immunology","year":2011,"id":675504,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1764972,"name":"Yukimi Sakoda","orcid":null,"position":1,"is_corresponding":false},{"id":1764973,"name":"JangJune Park","orcid":null,"position":2,"is_corresponding":false},{"id":1220374,"name":"Yuming Zhao","orcid":"0000-0002-1632-4646","position":3,"is_corresponding":false},{"id":1764971,"name":"Koji Tamada","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"BTLA-HVEM interaction delivers bidirectional signals and modulates the severity of GVHD (169.48)","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>B and T lymphocyte attenuator (BTLA), upon interaction with herpesvirus entry mediator (HVEM), delivers an inhibitory co-signal which regulates immune response in various diseases. In graft-versus-host disease (GVHD), unexpectedly, BTLA mediates positive effects on donor T cell survival, but immunological mechanisms of this function have yet to be fully explored. Our recent studies addressed a role of BTLA in GVHD by employing the newly established agonistic anti-BTLA mAb that stimulates BTLA signal without antagonizing BTLA-HVEM interaction. We revealed that BTLA signal inhibited donor anti-host T cell responses and ameliorated GVHD with a successful engraftment of donor hematopoietic cells. These effects were dependent on BTLA signal into donor T cells but neither donor non-T cells nor recipient cells. On the other hand, expression of BTLA mutant lacking an intracellular signaling domain restored impaired survival of BTLA-deficient T cells, suggesting that BTLA also serves as a ligand and delivers HVEM prosurvival co-signal in donor T cells. Thus, BTLA-HVEM interaction delivers positive and negative bidirectional co-signals to donor T cells via HVEM and BTLA, respectively, and modulates the severity of GVHD. Additional data obtained by recent studies will be also presented.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21097893","pmcid":null,"openalex_id":"https://openalex.org/W4313350045","authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"closed","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://academic.oup.com/jimmunol/article/186/1_Supplement/169.48/7982402","host_type":"publisher"},{"url":"https://doi.org/10.4049/jimmunol.186.supp.169.48","host_type":"journal"}],"fields_of_study":["Cytomegalovirus and herpesvirus research","Immune Cell Function and Interaction","Renal Transplantation Outcomes and Treatments"],"mesh_terms":[],"keywords":["BTLA","Immunology","Immune system","T cell","T lymphocyte","Cell biology","Biology","Chemistry"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T01:04:36.369006Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}