{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:51:34Z","timestamp":1792651894510,"version":"4.5.0"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T00:00:00Z","timestamp":1697414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Gold nanoparticles (GNPs) have been used in the development of novel therapies as a way of delivery of both stimulatory and tolerogenic peptide cargoes. Here we report that intradermal injection of GNPs loaded with the proinsulin peptide C19-A3, in patients with type 1 diabetes, results in recruitment and retention of immune cells in the skin. These include large numbers of clonally expanded T-cells sharing the same paired T-cell receptors (TCRs) with activated phenotypes, half of which, when the TCRs were re-expressed in a cell-based system, were confirmed to be specific for either GNP or proinsulin. All the identified gold-specific clones were CD8\n                    <jats:sup>+<\/jats:sup>\n                    , whilst proinsulin-specific clones were both CD8\n                    <jats:sup>+<\/jats:sup>\n                    and CD4\n                    <jats:sup>+<\/jats:sup>\n                    . Proinsulin-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    clones had a distinctive cytotoxic phenotype with overexpression of granulysin (GNLY) and KIR receptors. Clonally expanded antigen-specific T cells remained\n                    <jats:italic>in situ<\/jats:italic>\n                    for months to years, with a spectrum of tissue resident memory and effector memory phenotypes. As the T-cell response is divided between targeting the gold core and the antigenic cargo, this offers a route to improving resident memory T-cells formation in response to vaccines. In addition, our scRNAseq data indicate that focusing on clonally expanded skin infiltrating T-cells recruited to intradermally injected antigen is a highly efficient method to enrich and identify antigen-specific cells. This approach has the potential to be used to monitor the intradermal delivery of antigens and nanoparticles for immune modulation in humans.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2023.1276255","type":"journal-article","created":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T01:31:43Z","timestamp":1697419903000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Single-cell RNAseq identifies clonally expanded antigen-specific T-cells following intradermal injection of gold nanoparticles loaded with diabetes autoantigen in humans"],"prefix":"10.3389","volume":"14","author":[{"given":"Stephanie J.","family":"Hanna","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terri C.","family":"Thayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma J. 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