ThymoSpheres provide an innovative, user-friendly in vitro model for generating mature, predominantly CD8 single positive T cells. These cells resemble human polyclonal \u03b1\u03b2 unconventional T cells in transcriptome and TCR repertoire characteristics, making this model valuable for studying the development of this specific T-cell lineage.<\/p>\n
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In vitro cultures remain crucial for studying the fundamental mechanisms of human T-cell development. Here, we introduce a novel in vitro cultivation system based on ThymoSpheres (TS): dense spheroids consisting of DLL4-expressing stromal cells and human hematopoietic precursor cells, in the absence of thymic epithelial cells. These spheroids are subsequently cultured at the air\u2013liquid interphase. TS generate large numbers of mature T cells, are easy to manipulate, scalable, and can be repeatably sampled to monitor T-cell differentiation. The mature T cells generated from primary human hematopoietic precursor cells were extensively characterized using single-cell RNA and combined T-cell receptor (TCR) sequencing. These predominantly CD8\u03b1 T cells exhibit transcriptional and TCR CDR3 characteristics similar to the recently described human polyclonal \u03b1\u03b2 unconventional T cell (UTC) lineage. This includes the expression of hallmark genes associated with agonist selection, such as IKZF2 (Helios), and the expression of various natural killer receptors. The TCR repertoire of these UTCs is polyclonal and enriched for CDR3-associated autoreactive features and early rearrangements of the TCR-\u03b1 chain. In conclusion, TS cultures offer an intriguing platform to study the development of this human polyclonal UTC lineage and its inducing selection mechanisms.<\/p>","protected":false},"excerpt":{"rendered":"
ThymoSpheres provide an innovative, user-friendly in vitro model for generating mature, predominantly CD8 single positive T cells. These cells resemble human polyclonal \u03b1\u03b2 unconventional T cells in transcriptome and TCR repertoire characteristics, making this model valuable for studying the development of this specific T-cell lineage. Abstract In vitro cultures remain crucial for studying the fundamental … Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[112,42],"tags":[],"class_list":["post-16971","post","type-post","status-publish","format-standard","hentry","category-european-journal-of-immunology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/16971","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=16971"}],"version-history":[{"count":1,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/16971\/revisions"}],"predecessor-version":[{"id":16981,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/16971\/revisions\/16981"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=16971"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=16971"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=16971"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}