{"doi":"10.1182/blood.2022018440","title":"Prevention of acute GVHD using an orthogonal IL-2/IL-2Rβ system to selectively expand regulatory T cells in vivo","abstract":"Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative option for patients with hematological disorders and bone marrow (BM) failure syndromes. Graft-versus-host disease (GVHD) remains a leading cause of morbidity posttransplant. Regulatory T cell (Treg) therapies are efficacious in ameliorating GVHD but limited by variable suppressive capacities and the need for a high therapeutic dose. Here, we sought to expand Treg in vivo by expressing an orthogonal interleukin 2 receptor β (oIL-2Rβ) that would selectively interact with oIL-2 cytokine and not wild-type (WT) IL-2. To test whether the orthogonal system would preferentially drive donor Treg expansion, we used a murine major histocompatibility complex-disparate GVHD model of lethally irradiated BALB/c mice given T cell-depleted BM from C57BL/6 (B6) mice alone or together with B6Foxp3+GFP+ Treg or oIL-2Rβ-transduced Treg at low cell numbers that typically do not control GVHD with WT Treg. On day 2, B6 activated T cells (Tcons) were injected to induce GVHD. Recipients were treated with phosphate-buffered saline (PBS) or oIL-2 daily for 14 days, then 3 times weekly for an additional 14 days. Mice treated with oIL-2Rβ Treg and oIL-2 compared with those treated with PBS had enhanced GVHD survival, in vivo selective expansion of Tregs, and greater suppression of Tcon expansion in secondary lymphoid organs and intestines. Importantly, oIL-2Rβ Treg maintained graft-versus-tumor (GVT) responses in 2 distinct tumor models (A20 and MLL-AF9). These data demonstrate a novel approach to enhance the efficacy of Treg therapy in allo-HSCT using an oIL-2/oIL-2Rβ system that allows for selective in vivo expansion of Treg leading to GVHD protection and GVT maintenance.","journal":"Blood","year":2022,"id":247938,"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":32,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9584,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":649575,"name":"Sara Bolivar-Wagers","orcid":"0000-0002-6659-8194","position":1,"is_corresponding":false},{"id":471603,"name":"Sujeong Jin","orcid":"0000-0001-6504-3640","position":2,"is_corresponding":false},{"id":597280,"name":"Govindarajan Thangavelu","orcid":"0000-0003-3524-9570","position":3,"is_corresponding":false},{"id":299681,"name":"Federico Simonetta","orcid":"0000-0002-0399-689X","position":4,"is_corresponding":false},{"id":649573,"name":"Po‐Yu Lin","orcid":"0000-0002-2737-1544","position":5,"is_corresponding":false},{"id":649571,"name":"Toshihito Hirai","orcid":"0000-0002-3343-6674","position":6,"is_corresponding":false},{"id":597283,"name":"Asim Saha","orcid":"0000-0003-4721-2695","position":7,"is_corresponding":false},{"id":235911,"name":"Brent H. Koehn","orcid":"0000-0002-3669-2702","position":8,"is_corresponding":false},{"id":625421,"name":"Leon Su","orcid":"0000-0001-7654-9997","position":9,"is_corresponding":false},{"id":625479,"name":"Lora K. Picton","orcid":"0000-0002-0482-5187","position":10,"is_corresponding":false},{"id":459015,"name":"Jeanette Baker","orcid":"0000-0002-0753-0317","position":11,"is_corresponding":false},{"id":649574,"name":"Juliane K. Lohmeyer","orcid":"0000-0003-4311-0317","position":12,"is_corresponding":false},{"id":886264,"name":"Megan Riddle","orcid":"0000-0002-9557-217X","position":13,"is_corresponding":false},{"id":680140,"name":"Cindy Eide","orcid":"0000-0001-7314-2550","position":14,"is_corresponding":false},{"id":430835,"name":"Jakub Tolar","orcid":"0000-0002-0957-4380","position":15,"is_corresponding":false},{"id":488197,"name":"Angela Panoskaltsis‐Mortari","orcid":"0000-0003-1802-1785","position":16,"is_corresponding":false},{"id":241241,"name":"John E. Wagner","orcid":"0000-0003-1996-6262","position":17,"is_corresponding":false},{"id":218189,"name":"K. Christopher García","orcid":"0000-0001-9273-0278","position":18,"is_corresponding":false},{"id":412734,"name":"Robert S. Negrin","orcid":null,"position":19,"is_corresponding":false},{"id":52067,"name":"Bruce R. Blazar","orcid":"0000-0002-9608-9841","position":20,"is_corresponding":false},{"id":649572,"name":"Teresa Lopes Ramos","orcid":"0000-0002-0696-7197","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T00:23:57.824223Z","pmid":"36564052","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":[]}