{"doi":"10.3389/fimmu.2021.759706","title":"Editorial: Beyond Histocompatibility – Understanding the Non-MHC Determinants Shaping Transplantation Outcome and Tolerance Induction","abstract":"In seventy years, solid organ transplantation (SOTx) has progressed from a high-risk experimental procedure, with few recipients surviving into the 2nd year post-transplant, to becoming the standard of care for many end-stage organ diseases (1-3). During a similar period, allogeneic stem cell transplantation (AlloHCT) became a central treatment for malignancy and to correct lifethreatening lymphohematopoietic disorders (4). This success is due to the development of potent immunosuppressants that blunt T cell responses to major and minor histocompatibility complex (MHC) antigens, the dominant T cell targets after transplantation. Yet, numerous hurdles remain. Toxicities and side effects associated with general immunosuppression are well appreciated. Furthermore, while immunosuppression is a necessary evil after life sustaining SOTx, it is a roadblock for progress in the application of composite tissue allografts (CTA). Here, the side effects from the high doses of immunosuppression needed may outweigh the benefits to life quality provided. In both CTA and SOTx, even toxic levels of immunosuppressants are ineffective against the development of vasculopathy and fibrosis in solid organs over time (5). Finally, the combination of donor AlloHCT and SOTx has provided evidence that tolerance to donor antigens can be induced, yet the risk of graft-versus-host disease (GVHD) and unidentified barriers to routine tolerance induction with these protocols remain (6).","journal":"Frontiers in Immunology","year":2021,"id":221521,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":311638,"name":"Hēth Turnquist","orcid":"0000-0002-4173-4014","position":1,"is_corresponding":false},{"id":475624,"name":"Craig A. Byersdorfer","orcid":"0000-0002-0030-3699","position":0,"is_corresponding":true}],"reference_count":9,"raw_metadata":null,"created_at":"2026-07-18T23:53:55.215284Z","pmid":"34557204","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":[]}