{"doi":"10.3389/fimmu.2020.02180","title":"CD226 Deletion Reduces Type 1 Diabetes in the NOD Mouse by Impairing Thymocyte Development and Peripheral T Cell Activation","abstract":"The costimulatory molecule CD226 is highly expressed on effector/memory T cells and NK cells. Costimulatory signals received by T cells can impact both central and peripheral tolerance mechanisms. Genetic polymorphisms in CD226 have been associated with susceptibility to type 1 diabetes and other autoimmune diseases. We hypothesized that genetic deletion of Cd226 in the non-obese diabetic (NOD) mouse would impact type 1 diabetes incidence by altering T cell activation. CD226 knockout (KO) NOD mice displayed decreased disease incidence and insulitis in comparison to wild-type (WT) controls. Although female CD226 KO mice had similar levels of sialoadenitis as WT controls, male CD226 KO mice showed protection from dacryoadenitis. Moreover, CD226 KO T cells were less capable of adoptively transferring disease compared to WT NOD T cells. Of note, CD226 KO mice demonstrated increased CD8+ single positive (SP) thymocytes, leading to increased numbers of CD8+ T cells in the spleen. Decreased percentages of memory CD8+CD44+CD62L- T cells were observed in the pancreatic lymph nodes of CD226 KO mice. Intriguingly, CD8+ T cells in CD226 KO mice showed decreased islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-tetramer and CD5 staining, suggesting reduced T cell receptor affinity for this immunodominant antigen. These data support an important role for CD226 in type 1 diabetes development by modulating thymic T cell selection as well as impacting peripheral memory/effector CD8+ T cell activation and function.","journal":"Frontiers in Immunology","year":2020,"id":96684,"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":34,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9552,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":479038,"name":"Wen-I Yeh","orcid":"0000-0002-5705-4232","position":1,"is_corresponding":false},{"id":480048,"name":"Joshua R. Longfield","orcid":null,"position":2,"is_corresponding":false},{"id":479039,"name":"John T. Gallagher","orcid":"0009-0005-3758-0998","position":3,"is_corresponding":false},{"id":480049,"name":"Caridad M. Infante","orcid":null,"position":4,"is_corresponding":false},{"id":480050,"name":"Sarah Wellford","orcid":null,"position":5,"is_corresponding":false},{"id":251267,"name":"Amanda L. Posgai","orcid":"0000-0002-9491-0958","position":6,"is_corresponding":false},{"id":23929,"name":"Mark A. Atkinson","orcid":"0000-0001-8489-4782","position":7,"is_corresponding":false},{"id":251270,"name":"Martha Campbell‐Thompson","orcid":"0000-0001-6878-1235","position":8,"is_corresponding":false},{"id":296101,"name":"Scott M. Lieberman","orcid":"0000-0003-4082-7582","position":9,"is_corresponding":false},{"id":312736,"name":"David Serreze","orcid":null,"position":10,"is_corresponding":false},{"id":286498,"name":"Aron M. Geurts","orcid":"0000-0002-4347-2505","position":11,"is_corresponding":false},{"id":256321,"name":"Yi‐Guang Chen","orcid":"0000-0002-1741-9719","position":12,"is_corresponding":false},{"id":356521,"name":"Todd M. Brusko","orcid":"0000-0003-2878-9296","position":13,"is_corresponding":false},{"id":479037,"name":"Melanie R. Shapiro","orcid":"0000-0003-2090-0877","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-18T22:35:06.014648Z","pmid":"33013915","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":[]}