{"doi":"10.1038/15256","title":"Blocking both signal 1 and signal 2 of T-cell activation prevents apoptosis of alloreactive T cells and induction of peripheral allograft tolerance","abstract":null,"journal":"Nature Medicine","year":1999,"id":615552,"datarank":0.9932108477646203,"base_score":6.621405651764134,"endowment":6.621405651764134,"self_citation_contribution":0.9932108477646203,"citation_network_contribution":0.0,"self_endowment_contribution":0.9932108477646203,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":750,"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":1586694,"name":"Xian Chang Li","orcid":null,"position":1,"is_corresponding":false},{"id":1586695,"name":"Xin Xiao Zheng","orcid":null,"position":2,"is_corresponding":false},{"id":44539,"name":"Andrew D. Wells","orcid":"0000-0002-3630-2145","position":3,"is_corresponding":false},{"id":271013,"name":"Laurence A. Turka","orcid":"0000-0003-2104-6967","position":4,"is_corresponding":false},{"id":91615,"name":"Terry B. Strom","orcid":null,"position":5,"is_corresponding":false},{"id":251816,"name":"Yongsheng Li","orcid":"0000-0003-2175-9449","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Blocking both signal 1 and signal 2 of T-cell activation prevents apoptosis of alloreactive T cells and induction of peripheral allograft tolerance","abstract":"The alloimmune response against fully MHC-mismatched allografts, compared with immune responses to nominal antigens, entails an unusually large clonal size of alloreactive T cells. Thus, induction of peripheral allograft tolerance established in the absence of immune system ablation and reconstitution is a challenging task in transplantation. Here, we determined whether a reduction in the mass of alloreactive T cells due to apoptosis is an essential initial step for induction of stable allograft tolerance with non-lymphoablative therapy. Blocking both CD28-B7 and CD40-CD40 ligand interactions (co-stimulation blockade) inhibited proliferation of alloreactive T cells in vivo while allowing cell cycle-dependent T-cell apoptosis of proliferating T cells, with permanent engraftment of cardiac allografts but not skin allografts. Treatment with rapamycin plus co-stimulation blockade resulted in massive apoptosis of alloreactive T cells and produced stable skin allograft tolerance, a very stringent test of allograft tolerance. In contrast, treatment with cyclosporine A and co-stimulation blockade abolished T-cell proliferation and apoptosis, as well as the induction of stable allograft tolerance. Our data indicate that induction of T-cell apoptosis and peripheral allograft tolerance is prevented by blocking both signal 1 and signal 2 of T-cell activation.","is_dataset_classified":null,"base_score":6.621405651764134,"endowment":6.621405651764134,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10545997","pmcid":null,"openalex_id":"https://openalex.org/W2019291297","authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"R01AI42298","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"P01 AI041521","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"P0 AI/GF 41521","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01AI042298-02","title":"NON T CELL PRODUCED NOVEL T CELL GROWTH FACTORS"}],"total_grants":4,"fwci":22.0802,"citation_percentile":0.99756535,"influential_citations":0,"citation_trend":[{"year":2012,"count":19},{"year":2013,"count":19},{"year":2014,"count":16},{"year":2015,"count":24},{"year":2016,"count":8},{"year":2017,"count":7},{"year":2018,"count":7},{"year":2019,"count":10},{"year":2020,"count":8},{"year":2021,"count":4},{"year":2022,"count":4},{"year":2023,"count":9},{"year":2024,"count":4},{"year":2025,"count":3}],"oa_status":"closed","license":"Springer TDM","oa_locations":[{"url":"http://www.nature.com/articles/nm1199_1298","host_type":"publisher"},{"url":"http://www.nature.com/articles/nm1199_1298.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1038/15256","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10545997","host_type":"repository"},{"url":"https://dx.doi.org/10.1038/15256","host_type":""}],"fields_of_study":["T-cell and B-cell Immunology","Immune Cell Function and Interaction","Immunotherapy and Immune Responses","03 medical and health sciences","0302 clinical medicine","Adaptation, Physiological","Animals","Apoptosis","Cell Division","Graft Survival","Lymphocyte Activation","Mice","Mice, Inbred Strains","Signal Transduction","T-Lymphocytes"],"mesh_terms":["Adaptation, Physiological","Animals","Cell Division","Graft Survival","Lymphocyte Activation","Mice, Inbred Strains","T-Lymphocytes","Signal Transduction","Apoptosis","Mice"],"keywords":["Immune tolerance","Peripheral tolerance","CD28","T cell","Apoptosis","Blockade","Clonal deletion","Transplantation","Immunology","Biology","Immune system","Cell biology","T-cell receptor","Cancer research","Receptor","Medicine","Internal medicine","Mice","T-Lymphocytes","Graft Survival","Animals","Mice, Inbred Strains","Lymphocyte Activation","Adaptation, Physiological","Cell Division","Signal Transduction"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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