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We recently discovered an unexpected CD4+ and CD8\u03b1\u03b2+ immune cell population in healthy and atherosclerotic mice by single-cell RNA sequencing. Transcriptomically, these cells resembled thymic DPs. Flow cytometry and three-dimensional whole-mount imaging confirmed DPs in thymus, mediastinal adipose tissue, and aortic adventitia, but nowhere else. Deep transcriptional profiling revealed differences between DP cells isolated from the three locations. All DPs were dependent on RAG2 expression and the presence of the thymus. Mediastinal adipose tissue DPs resided in close vicinity to invariant NKT cells, which they could activate in vitro. Thymus transplantation failed to reconstitute extrathymic DPs, and frequencies of extrathymic DPs were unaltered by pharmacologic inhibition of S1P1, suggesting that their migration may be locally confined. Our results define two new, transcriptionally distinct subsets of extrathymic DPs that may play a role in aortic vascular homeostasis.<\/jats:p>","DOI":"10.4049\/jimmunol.2100208","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T16:55:14Z","timestamp":1636131314000},"page":"2720-2732","source":"Crossref","is-referenced-by-count":6,"title":["Thymus-Derived CD4+CD8+ Cells Reside in Mediastinal Adipose Tissue and the Aortic Arch"],"prefix":"10.1093","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1333-2031","authenticated-orcid":false,"given":"Holger","family":"Winkels","sequence":"first","affiliation":[{"name":"La Jolla Institute for Immunology , La Jolla, CA"},{"name":"Department of Cardiology, Clinic III for Internal Medicine, University of Cologne , Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanal","family":"Ghosheh","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Immunology , La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kouji","family":"Kobiyama","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Immunology , La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William B","family":"Kiosses","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Immunology , La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Orecchioni","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Immunology , La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2823-439X","authenticated-orcid":false,"given":"Erik","family":"Ehinger","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Immunology , La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasantika","family":"Suryawanshi","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Immunology , La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9519-9520","authenticated-orcid":false,"given":"Sara","family":"Herrera-De La Mata","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Immunology , La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Marchovecchio","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Immunology , La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0372-5272","authenticated-orcid":false,"given":"Thomas","family":"Riffelmacher","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Immunology , La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Thiault","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Immunology , La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell","family":"Kronenberg","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Immunology , La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1525-4348","authenticated-orcid":false,"given":"Dennis","family":"Wolf","sequence":"additional","affiliation":[{"name":"University Hospital Freiburg , Freiburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8164-6852","authenticated-orcid":false,"given":"Gregory","family":"Seumois","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Immunology , La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pandurangan","family":"Vijayanand","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Immunology , La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9339-3672","authenticated-orcid":false,"given":"Klaus","family":"Ley","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Immunology , La Jolla, CA"},{"name":"Department of Bioengineering, University of California , San Diego, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,12,1]]},"reference":[{"key":"2025022610323483300_r1","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1161\/CIRCRESAHA.118.313591","article-title":"Immunity and inflammation in atherosclerosis","volume":"124","author":"Wolf","year":"2019","journal-title":"Circ. 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