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Because the islets of Langerhans are insulated from blood vessels by a double basement membrane and lack detectable lymphatic drainage, interactions between endocrine and circulating T cells are not permitted. Thus, we hypothesized that initiation and progression of anti-islet immunity required islet neolymphangiogenesis to allow T cell access to the islet. Combining microscopy and single cell approaches, the timing of this phenomenon in mice was situated between 5 and 8 wk of age when activated anti-insulin CD4 T cells became detectable in peripheral blood while peri-islet pathology developed. This \u201cperi-insulitis,\u201d dominated by CD4 T cells, respected the islet basement membrane and was limited on the outside by lymphatic endothelial cells that gave it the attributes of a tertiary lymphoid structure. As in most tissues, lymphangiogenesis seemed to be secondary to local segmental endothelial inflammation at the collecting postcapillary venule. In addition to classic markers of inflammation such as CD29, V-CAM, and NOS, MHC class II molecules were expressed by nonhematopoietic cells in the same location both in mouse and human islets. This CD45\u2212 MHC class II+ cell population was capable of spontaneously presenting islet Ags to CD4 T cells. Altogether, these observations favor an alternative model for the initiation of T1D, outside of the islet, in which a vascular-associated cell appears to be an important MHC class II\u2013expressing and \u2013presenting cell.<\/jats:p>","DOI":"10.4049\/jimmunol.2300769","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T15:00:02Z","timestamp":1709305202000},"page":"1094-1104","source":"Crossref","is-referenced-by-count":5,"title":["Repositioning the Early Pathology of Type 1 Diabetes to the Extraislet Vasculature"],"prefix":"10.1093","volume":"212","author":[{"given":"Anne","family":"Costanzo","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute , La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1917-1566","authenticated-orcid":false,"given":"Don","family":"Clarke","sequence":"additional","affiliation":[{"name":"Department of 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Clin. Invest."},{"key":"2025020405471888600_r44","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.4049\/jimmunol.1501570","article-title":"Tertiary lymphoid tissue forms in retinas of mice with spontaneous autoimmune uveitis and has consequences on visual function","volume":"196","author":"Kielczewski","year":"2016","journal-title":"J. Immunol."},{"key":"2025020405471888600_r45","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1126\/science.424741","article-title":"Multiple sclerosis: presence of lymphatic capillaries and lymphoid tissue in the brain and spinal cord","volume":"203","author":"Prineas","year":"1979","journal-title":"Science"},{"key":"2025020405471888600_r46","doi-asserted-by":"crossref","first-page":"451","DOI":"10.3389\/fimmu.2016.00451","article-title":"Tertiary lymphoid organs in central nervous system autoimmunity","volume":"7","author":"Mitsdoerffer","year":"2016","journal-title":"Front. 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Haemost."},{"key":"2025020405471888600_r75","doi-asserted-by":"crossref","first-page":"44S","DOI":"10.1016\/S0895-7061(01)02069-6","article-title":"Adhesion molecules and their role in vascular disease","volume":"14","author":"Krieglstein","year":"2001","journal-title":"Am. J. Hypertens."},{"key":"2025020405471888600_r76","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1073\/pnas.1018975108","article-title":"Entry of diabetogenic T cells into islets induces changes that lead to amplification of the cellular response","volume":"108","author":"Calderon","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025020405471888600_r77","doi-asserted-by":"crossref","first-page":"2800","DOI":"10.3389\/fimmu.2018.02800","article-title":"IFN\u03b3-induced MHC class II expression on islet endothelial cells is an early marker of insulitis but is not required for diabetogenic CD4+ T cell migration","volume":"9","author":"Scott","year":"2018","journal-title":"Front. 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(Landmark Ed.)"},{"key":"2025020405471888600_r79","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/s41586-021-04183-x","article-title":"Exercise plasma boosts memory and dampens brain inflammation via clusterin","volume":"600","author":"De Miguel","year":"2021","journal-title":"Nature"},{"key":"2025020405471888600_r80","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/329599a0","article-title":"HLA-DQ\u03b2 gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus","volume":"329","author":"Todd","year":"1987","journal-title":"Nature"},{"key":"2025020405471888600_r81","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1038\/ng.3353","article-title":"Additive and interaction effects at three amino acid positions in HLA-DQ and HLA-DR molecules drive type 1 diabetes risk","volume":"47","author":"Hu","year":"2015","journal-title":"Nat. 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