Single-cell RNAseq identifies clonally expanded antigen-specific T-cells following intradermal injection of gold nanoparticles loaded with diabetes autoantigen in humans.


Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2023
Historique:
received: 11 08 2023
accepted: 02 10 2023
medline: 2 11 2023
pubmed: 1 11 2023
entrez: 1 11 2023
Statut: epublish

Résumé

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

Identifiants

pubmed: 37908349
doi: 10.3389/fimmu.2023.1276255
pmc: PMC10613693
doi:

Substances chimiques

Autoantigens 0
Proinsulin 9035-68-1
Gold 7440-57-5
Peptides 0
Receptors, Antigen, T-Cell 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1276255

Informations de copyright

Copyright © 2023 Hanna, Thayer, Robinson, Vinh, Williams, Landry, Andrews, Siah, Leete, Wyatt, McAteer, Nakayama, Wong, Yang, Tree, Ludvigsson, Dayan and Tatovic.

Déclaration de conflit d'intérêts

CD has lectured for or been involved as an advisor to the following companies: Novonordisk, Sanofi-genzyme, Janssen, Servier, Lilly, Astrazeneca, Provention Bio, UCB, MSD, Vielo Bio, Avotres, Worg, Novartis. CD holds a patent jointly with Midatech plc and Provention Bio/Sanofi. DT is a Trustee for NovoNordisk UK Research Foundation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Stephanie J Hanna (SJ)

Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom.

Terri C Thayer (TC)

Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom.
Department of Biological and Chemical Sciences, Roberts Wesleyan University, Rochester, NY, United States.

Emma J S Robinson (EJS)

Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom.

Ngoc-Nga Vinh (NN)

Division of Psychological Medicine and Clinical Neurosciences, Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom.

Nigel Williams (N)

Division of Psychological Medicine and Clinical Neurosciences, Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom.

Laurie G Landry (LG)

Barbara Davis Center for Childhood Diabetes, University of Colorado, Denver, CO, United States.

Robert Andrews (R)

Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom.

Qi Zhuang Siah (QZ)

John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, United Kingdom.

Pia Leete (P)

Department of Clinical and Biomedical Sciences, University of Exeter, Exeter, United Kingdom.

Rebecca Wyatt (R)

Department of Clinical and Biomedical Sciences, University of Exeter, Exeter, United Kingdom.

Martina A McAteer (MA)

Department of Oncology, University of Oxford, Oxford, United Kingdom.

Maki Nakayama (M)

Barbara Davis Center for Childhood Diabetes, University of Colorado, Denver, CO, United States.

F Susan Wong (FS)

Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom.

Jennie H M Yang (JHM)

Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, Guy's Hospital, London, United Kingdom.

Timothy I M Tree (TIM)

Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, Guy's Hospital, London, United Kingdom.

Johnny Ludvigsson (J)

Division of Pediatrics, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences and Crown Princess Victoria Children´s Hospital, Linköping University, Linköping, Sweden.

Colin M Dayan (CM)

Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom.

Danijela Tatovic (D)

Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom.

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