{"doi":"10.4049/jimmunol.1900357","title":"Insulin Receptor–Expressing T Cells Appear in Individuals at Risk for Type 1 Diabetes and Can Move into the Pancreas in C57BL/6 Transgenic Mice","abstract":"Abstract Insulin receptor (IR) expression on the T cell surface can indicate an activated state; however, the IR is also chemotactic, enabling T cells with high IR expression to physically move toward insulin. In humans with type 1 diabetes (T1D) and the NOD mouse model, a T cell–mediated autoimmune destruction of insulin-producing pancreatic β cells occurs. In previous work, when purified IR+ and IR− T cells were sorted from diabetic NOD mice and transferred into irradiated nondiabetic NOD mice, only those that received IR+ T cells developed insulitis and diabetes. In this study, peripheral blood samples from individuals with T1D (new onset to 14 y of duration), relatives at high-risk for T1D, defined by positivity for islet autoantibodies, and healthy controls were examined for frequency of IR+ T cells. High-risk individuals had significantly higher numbers of IR+ T cells as compared with those with T1D (p < 0.01) and controls (p < 0.001); however, the percentage of IR+ T cells in circulation did not differ significantly between T1D and control subjects. With the hypothesis that IR+ T cells traffic to the pancreas in T1D, we developed a (to our knowledge) novel mouse model exhibiting a FLAG-tagged mouse IR on T cells on the C57BL/6 background, which is not susceptible to developing T1D. Interestingly, these C57BL/6-CD3FLAGmIR/mfm mice showed evidence of increased IR+ T cell trafficking into the islets compared with C57BL/6 controls (p < 0.001). This transgenic animal model provides a (to our knowledge) novel platform for investigating the influence of IR expression on T cell trafficking and the development of insulitis.","journal":"The Journal of Immunology","year":2021,"id":210968,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9556,"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":571724,"name":"Emily Esakov","orcid":null,"position":1,"is_corresponding":false},{"id":301095,"name":"Brigid Gregg","orcid":"0000-0002-1192-2997","position":2,"is_corresponding":false},{"id":23929,"name":"Mark A. Atkinson","orcid":"0000-0001-8489-4782","position":3,"is_corresponding":false},{"id":800452,"name":"Douglas G. Rogers","orcid":null,"position":4,"is_corresponding":false},{"id":800453,"name":"James D. Horner","orcid":null,"position":5,"is_corresponding":false},{"id":409337,"name":"Kanakadurga Singer","orcid":"0000-0001-8278-3800","position":6,"is_corresponding":false},{"id":355135,"name":"Steven K. Lundy","orcid":"0000-0002-3655-2216","position":7,"is_corresponding":false},{"id":428128,"name":"Jamie L. Felton","orcid":"0000-0002-6170-1156","position":8,"is_corresponding":false},{"id":799846,"name":"Tasneem Al-Huniti","orcid":"0000-0002-0731-928X","position":9,"is_corresponding":false},{"id":353749,"name":"Andrea L. Nestor‐Kalinoski","orcid":"0000-0002-1475-3578","position":10,"is_corresponding":false},{"id":611469,"name":"Michael P. Morran","orcid":null,"position":11,"is_corresponding":false},{"id":799847,"name":"Nirdesh K. Gupta","orcid":"0000-0001-9787-9645","position":12,"is_corresponding":false},{"id":799848,"name":"James D. Bretz","orcid":"0000-0001-9659-439X","position":13,"is_corresponding":false},{"id":716266,"name":"Swapnaa Balaji","orcid":null,"position":14,"is_corresponding":false},{"id":799849,"name":"Tian Chen","orcid":"0000-0001-8490-600X","position":15,"is_corresponding":false},{"id":704815,"name":"Marcia F. McInerney","orcid":"0000-0001-9348-2480","position":16,"is_corresponding":false},{"id":800451,"name":"Neha Nandedkar-Kulkarni","orcid":null,"position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-18T23:52:16.049481Z","pmid":"33658296","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":[]}