{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:16:42Z","timestamp":1792451802022,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,11,25]],"date-time":"2020-11-25T00:00:00Z","timestamp":1606262400000},"content-version":"vor","delay-in-days":329,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp;amp; Trans Imm"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Genetic or acquired defects in FOXP3<jats:sup>+<\/jats:sup> regulatory T cells (Tregs) play a key role in many immune\u2010mediated diseases including immune dysregulation polyendocrinopathy, enteropathy, X\u2010linked (IPEX) syndrome. Previously, we demonstrated CD4<jats:sup>+<\/jats:sup> T cells from healthy donors and IPEX patients can be converted into functional Treg\u2010like cells by lentiviral transfer of <jats:italic>FOXP3<\/jats:italic> (CD4<jats:sup>LVFOXP3<\/jats:sup>). These CD4<jats:sup>LVFOXP3<\/jats:sup> cells have potent regulatory function, suggesting their potential as an innovative therapeutic. Here, we present molecular and preclinical <jats:italic>in vivo<\/jats:italic> data supporting CD4<jats:sup>LVFOXP3<\/jats:sup> cell clinical progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The molecular characterisation of CD4<jats:sup>LVFOXP3<\/jats:sup> cells included flow cytometry, qPCR, RNA\u2010seq and TCR\u2010seq. The <jats:italic>in vivo<\/jats:italic> suppressive function of CD4<jats:sup>LVFOXP3<\/jats:sup> cells was assessed in xenograft\u2010versus\u2010host disease (xeno\u2010GvHD) and FOXP3\u2010deficient IPEX\u2010like humanised mouse models. The safety of CD4<jats:sup>LVFOXP3<\/jats:sup> cells was evaluated using peripheral blood (PB) humanised (hu)\u2010 mice testing their impact on immune response against pathogens, and immune surveillance against tumor antigens.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We demonstrate that the conversion of CD4<jats:sup>+<\/jats:sup> T cells to CD4<jats:sup>LVFOXP3<\/jats:sup> cells leads to specific transcriptional changes as compared to CD4<jats:sup>+<\/jats:sup> T\u2010cell transduction in the absence of FOXP3, including upregulation of Treg\u2010related genes. Furthermore, we observe specific preservation of a polyclonal TCR repertoire during <jats:italic>in vitro<\/jats:italic> cell production. Both allogeneic and autologous CD4<jats:sup>LVFOXP3<\/jats:sup> cells protect from xeno\u2010GvHD after two sequential infusions of effector T cells. CD4<jats:sup>LVFOXP3<\/jats:sup> cells prevent hyper\u2010proliferation of CD4<jats:sup>+<\/jats:sup> memory T cells in the FOXP3\u2010deficient IPEX\u2010like hu\u2010mice. CD4<jats:sup>LVFOXP3<\/jats:sup> cells do not impede <jats:italic>in vivo<\/jats:italic> expansion of antigen\u2010primed T cells or tumor clearance in the PB hu\u2010mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data support the clinical readiness of CD4<jats:sup>LVFOXP3<\/jats:sup> cells to treat IPEX syndrome and other immune\u2010mediated diseases caused by insufficient or dysfunctional FOXP3<jats:sup>+<\/jats:sup> Tregs.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cti2.1214","type":"journal-article","created":{"date-parts":[[2020,11,26]],"date-time":"2020-11-26T00:24:06Z","timestamp":1606350246000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Human\u2010engineered Treg\u2010like cells suppress FOXP3\u2010deficient T cells but preserve adaptive immune responses <i>in vivo<\/i>"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8042-0069","authenticated-orcid":false,"given":"Yohei","family":"Sato","sequence":"first","affiliation":[{"name":"Department of Pediatrics Division of Hematology, Oncology Stem Cell Transplantation and Regenerative Medicine Stanford University School of Medicine Stanford CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Passerini","sequence":"additional","affiliation":[{"name":"Mechanisms of Peripheral Tolerance Unit San Raffaele Telethon Institute for Gene Therapy (SR\u2010TIGET) IRCCS San Raffaele Scientific Institute Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian D","family":"Piening","sequence":"additional","affiliation":[{"name":"Earle A Chiles Research Institute Providence Portland Medical Center Portland OR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly Javier","family":"Uyeda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Hematology, Oncology Stem Cell Transplantation and Regenerative Medicine Stanford University School of Medicine Stanford CA USA"},{"name":"Institute for Stem Cell Biology and Regenerative Medicine Stanford University School of Medicine Stanford CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Goodwin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Hematology, Oncology Stem Cell Transplantation and Regenerative Medicine Stanford University School of Medicine Stanford CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Gregori","sequence":"additional","affiliation":[{"name":"Mechanisms of Peripheral Tolerance Unit San Raffaele Telethon Institute for Gene Therapy (SR\u2010TIGET) IRCCS San Raffaele Scientific Institute Milan 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