{"doi":"10.1084/jem.183.4.1657","title":"Breaking self-tolerance in nonobese diabetic mice.","abstract":"<jats:p>Unresponsiveness to self is maintained through two mechanisms of immune regulation: thymic-negative selection and peripheral tolerance. Although thymic-negative selection is a major mechanism to eliminate self-reactive T cells, normal mice have readily detectable populations of T cells reactive to self-proteins but do not exhibit autoimmune responses. It has been postulated that autoimmune disease results from breakdown or loss of peripheral tolerance. We present data that demonstrate that peripheral tolerance or unresponsiveness to self can be broken in nonobese diabetic (NOD) mice. Immunization of NOD mice (but not of conventional mice) with self-peptides caused an immune response to self-peptide with resultant autoproliferation of peripheral lymphocytes. Autoproliferation of self-reactive T cells in NOD mice resulted from the recognition and proliferation of the activated T cells to endogenously processed and presented self-antigens. This loss of self-tolerance demonstrated in vitro may well be the basis of NOD autoimmune disease in vivo.</jats:p>","journal":"The Journal of experimental medicine","year":1996,"id":602707,"datarank":0.6716005221717312,"base_score":4.477336814478207,"endowment":4.477336814478207,"self_citation_contribution":0.6716005221717312,"citation_network_contribution":0.0,"self_endowment_contribution":0.6716005221717312,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":87,"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":1545867,"name":"M Fassò","orcid":null,"position":1,"is_corresponding":false},{"id":1545868,"name":"A Lanctot","orcid":null,"position":2,"is_corresponding":false},{"id":1545870,"name":"C Garvey","orcid":null,"position":3,"is_corresponding":false},{"id":1545871,"name":"C G Fathman","orcid":null,"position":4,"is_corresponding":false},{"id":1545866,"name":"W M Ridgway","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Breaking self-tolerance in nonobese diabetic mice.","abstract":"<jats:p>Unresponsiveness to self is maintained through two mechanisms of immune regulation: thymic-negative selection and peripheral tolerance. Although thymic-negative selection is a major mechanism to eliminate self-reactive T cells, normal mice have readily detectable populations of T cells reactive to self-proteins but do not exhibit autoimmune responses. It has been postulated that autoimmune disease results from breakdown or loss of peripheral tolerance. We present data that demonstrate that peripheral tolerance or unresponsiveness to self can be broken in nonobese diabetic (NOD) mice. Immunization of NOD mice (but not of conventional mice) with self-peptides caused an immune response to self-peptide with resultant autoproliferation of peripheral lymphocytes. Autoproliferation of self-reactive T cells in NOD mice resulted from the recognition and proliferation of the activated T cells to endogenously processed and presented self-antigens. This loss of self-tolerance demonstrated in vitro may well be the basis of NOD autoimmune disease in vivo.</jats:p>","is_dataset_classified":null,"base_score":4.477336814478207,"endowment":4.477336814478207,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"8666923","pmcid":"PMC2192523","openalex_id":"https://openalex.org/W2143429830","authors":[],"funders":[{"funder_name":"NIDDK NIH HHS","grant_id":"DK-44837","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"DK-39959","title":null}],"total_grants":2,"fwci":5.6433,"citation_percentile":0.96494387,"influential_citations":0,"citation_trend":[{"year":2013,"count":2},{"year":2016,"count":1},{"year":2018,"count":1},{"year":2021,"count":3}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://rupress.org/jem/article-pdf/183/4/1657/1108107/1657.pdf","host_type":"journal"},{"url":"https://rupress.org/jem/article-pdf/183/4/1657/1108107/1657.pdf","host_type":"publisher"},{"url":"https://rupress.org/jem/article-pdf/183/4/1657/1678845/1657.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1084/jem.183.4.1657","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/8666923","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2192523","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC2192523","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC2192523?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Diabetes and associated disorders","Diabetes Management and Research","Celiac Disease Research and Management"],"mesh_terms":["Amino Acid Sequence","Animals","Histocompatibility Antigens Class II","Autoimmune Diseases","Immunization","Lymphocyte Activation","Mice, Inbred DBA","Molecular Sequence Data","Myoglobin","Peptide Fragments","Species Specificity","CD4-Positive T-Lymphocytes","Mice, Inbred NOD","Self Tolerance","Mice"],"keywords":["Peripheral tolerance","Nod","Self Tolerance","NOD mice","Immune tolerance","Negative selection","Clonal deletion","Immunology","Immune system","Central tolerance","Antigen","Biology","Autoimmune disease","Autoimmunity","T cell","Antibody","Diabetes mellitus","Endocrinology","T-cell receptor"],"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":"2026-07-29T20:05:38.660598Z","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":[]}