دورية أكاديمية
Single-cell RNAseq identifies clonally expanded antigen-specific T-cells following intradermal injection of gold nanoparticles loaded with diabetes autoantigen in humans
| العنوان: | Single-cell RNAseq identifies clonally expanded antigen-specific T-cells following intradermal injection of gold nanoparticles loaded with diabetes autoantigen in humans |
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| المؤلفون: | Hanna, Stephanie J., Thayer, Terri C., Robinson, Emma J. S., Vinh, Ngoc-Nga, Williams, Nigel, Landry, Laurie G., Andrews, Robert, Siah, Qi Zhuang, Leete, Pia, Wyatt, Rebecca, McAteer, Martina A., Nakayama, Maki, Wong, F. Susan, Yang, Jennie H. M., Tree, Timothy I. M., Ludvigsson, Johnny, Dayan, Colin M., Tatovic, Danijela |
| بيانات النشر: | Frontiers Media |
| سنة النشر: | 2023 |
| المجموعة: | Cardiff University: ORCA (Online Research @ Cardiff) |
| الوصف: | 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+, whilst proinsulin-specific clones were both CD8+ and CD4+. Proinsulin-specific CD8+ clones had a distinctive cytotoxic phenotype with overexpression of granulysin (GNLY) and KIR receptors. Clonally expanded antigen-specific T cells remained in situ 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://orca.cardiff.ac.uk/id/eprint/163574/1/DataSheet_1.pdfTest; https://orca.cardiff.ac.uk/id/eprint/163574/2/fimmu-14-1276255.pdfTest; Hanna, Stephanie J. https://orca.cardiff.ac.uk/view/cardiffauthors/A222750B.htmlTest, Thayer, Terri C., Robinson, Emma J. S. https://orca.cardiff.ac.uk/view/cardiffauthors/A2157380B.htmlTest, Vinh, Ngoc-Nga https://orca.cardiff.ac.uk/view/cardiffauthors/A004260M.htmlTest, Williams, Nigel https://orca.cardiff.ac.uk/view/cardiffauthors/A0001924.htmlTest orcid:0000-0003-1177-6931 orcid:0000-0003-1177-6931, Landry, Laurie G., Andrews, Robert https://orca.cardiff.ac.uk/view/cardiffauthors/A1536713J.htmlTest, Siah, Qi Zhuang, Leete, Pia, Wyatt, Rebecca, McAteer, Martina A., Nakayama, Maki, Wong, F. Susan https://orca.cardiff.ac.uk/view/cardiffauthors/A189149P.htmlTest orcid:0000-0002-2812-8845 orcid:0000-0002-2812-8845, Yang, Jennie H. M., Tree, Timothy I. M., Ludvigsson, Johnny, Dayan, Colin M. https://orca.cardiff.ac.uk/view/cardiffauthors/A192115G.htmlTest orcid:0000-0002-6557-3462 orcid:0000-0002-6557-3462 and Tatovic, Danijela https://orca.cardiff.ac.uk/view/cardiffauthors/A2886703.htmlTest orcid:0000-0002-3879-2686 orcid:0000-0002-3879-2686 2023. Single-cell RNAseq identifies clonally expanded antigen-specific T-cells following intradermal injection of gold nanoparticles loaded with diabetes autoantigen in humans. Frontiers in Immunology 14 , 1276255. 10.3389/fimmu.2023.1276255 https://doi.org/10.3389/fimmu.2023.1276255Test file https://orca.cardiff.ac.uk/id/eprint/163574/1/DataSheet_1.pdffileTest https://orca.cardiff.ac.uk/id/eprint/163574/2/fimmu-14-1276255.pdfTest |
| DOI: | 10.3389/fimmu.2023.1276255 |
| الإتاحة: | https://doi.org/10.3389/fimmu.2023.1276255Test https://orca.cardiff.ac.uk/id/eprint/163574Test/ https://orca.cardiff.ac.uk/id/eprint/163574/1/DataSheet_1.pdfTest https://orca.cardiff.ac.uk/id/eprint/163574/2/fimmu-14-1276255.pdfTest |
| حقوق: | cc_by_4_0 |
| رقم الانضمام: | edsbas.677E0451 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fimmu.2023.1276255 |
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