{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:13:23Z","timestamp":1772990003140,"version":"3.50.1"},"reference-count":53,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T00:00:00Z","timestamp":1700611200000},"content-version":"vor","delay-in-days":325,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019408","name":"Marcus Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019408","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp; Trans Imm"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Thymus implantation is a recently FDA\u2010approved therapy for congenital athymia. Patients receiving thymus implantation develop a functional but incomplete T cell compartment. Our objective was to develop a mouse model to study clinical thymus implantation in congenital athymia and to optimise implantation procedures to maximise T cell education and expansion of na\u00efve T cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using <jats:italic>Foxn1<\/jats:italic><jats:sup>nu<\/jats:sup> athymic mice as recipients, we tested MHC\u2010matched and \u2010mismatched donor thymi that were implanted as fresh tissue or cultured to remove donor T\u00a0cells. We first implanted thymus under the kidney capsule and then optimised intramuscular implantation. Using competitive adoptive transfer assays, we investigated whether the failure of newly developed T cells to expand into a complete T cell compartment was because of intrinsic deficits or whether there were deficits in engaging MHC molecules in the periphery. Finally, we tested whether recombinant IL\u20107 would promote the expansion of host na\u00efve T cells educated by the implanted thymus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We determined that thymus implants in <jats:italic>Foxn1<\/jats:italic><jats:sup>nu<\/jats:sup> athymic mice mimic many aspects of clinical thymus implants in patients with congenital athymia. When we implanted cultured, MHC\u2010mismatched donor thymus into <jats:italic>Foxn1<\/jats:italic><jats:sup>nu<\/jats:sup> athymic mice, mice developed a limited T cell compartment with notably underdeveloped na\u00efve populations and overrepresented memory\u2010like T cells. Newly generated T cells were predominantly educated by MHC molecules expressed by the donor thymus, thus potentially undergoing another round of selection once in the peripheral circulation. Using competitive adoptive transfer assays, we compared expansion rates of T cells educated on donor thymus <jats:italic>versus<\/jats:italic> T cells educated during typical thymopoiesis in MHC\u2010matched and \u2010mismatched environments. Once in the circulation, regardless of the MHC haplotypes, T cells educated on a donor thymus underwent abnormal expansion with initially more robust proliferation coupled with greater cell death, resembling IL\u20107 independent spontaneous expansion. Treating implanted mice with recombinant interleukin (IL\u20107) promoted homeostatic expansion that improved T cell development, expanded the T cell receptor repertoire, and normalised the na\u00efve T cell compartment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We conclude that implanting cultured thymus into the muscle of <jats:italic>Foxn1<\/jats:italic><jats:sup>nu<\/jats:sup> athymic mice is an appropriate system to study thymus implantation for congenital athymia and immunodeficiencies. T cells are educated by the donor thymus, yet na\u00efve T cells have deficits in expansion. IL\u20107 greatly improves T cell development after thymus implantation and may offer a novel strategy to improve outcomes of clinical thymus implantation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cti2.1475","type":"journal-article","created":{"date-parts":[[2023,11,25]],"date-time":"2023-11-25T00:02:29Z","timestamp":1700870549000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Improving thymus implantation for congenital athymia with interleukin\u20107"],"prefix":"10.1002","volume":"12","author":[{"given":"Hyunjung","family":"Min","sequence":"first","affiliation":[{"name":"Marcus Center for Cellular Cures Duke University  Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura A","family":"Valente","sequence":"additional","affiliation":[{"name":"Marcus Center for Cellular Cures Duke University  Durham NC USA"},{"name":"Department of Pathology Duke University  Durham NC 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