Non-invasive multiphoton imaging of islets transplanted into the pinna of the NOD mouse ear reveals the immediate effect of anti-CD3 treatment in autoimmune diabetes

Benson, R. A. et al. (2018) Non-invasive multiphoton imaging of islets transplanted into the pinna of the NOD mouse ear reveals the immediate effect of anti-CD3 treatment in autoimmune diabetes. Frontiers in Immunology, 9, 1006. (doi: 10.3389/fimmu.2018.01006) (PMID:29867981) (PMCID:PMC5968092)

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Abstract

We present a novel and readily accessible method facilitating cellular time-resolved imaging of transplanted pancreatic islets. Grafting of islets to the mouse ear pinna allows non-invasive, in vivo longitudinal imaging of events in the islets and enables improved acquisition of experimental data and use of fewer experimental animals than is possible using invasive techniques, as the same mouse can be assessed for the presence of islet infiltrating cells before and after immune intervention. We have applied this method to investigating therapeutic protection of beta cells through the well-established use of anti-CD3 injection, and have acquired unprecedented data on the nature and rapidity of the effect on the islet infiltrating T cells. We demonstrate that infusion of anti-CD3 antibody leads to immediate effects on islet infiltrating T cells in islet grafts in the pinna of the ear, and causes them to increase their speed and displacement within 20 min of infusion. This technique overcomes several technical challenges associated with intravital imaging of pancreatic immune responses and facilitates routine study of beta islet cell development, differentiation, and function in health and disease.

Item Type:Articles
Keywords:Immunotherapy, multiphoton, T cell, islets, autoimmunity, imaging, type 1 diabetes, anti-cd3.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Garside, Professor Paul and Brewer, Professor James and Benson, Dr Robert
Authors: Benson, R. A., Garcon, F., Recino, A., Ferdinand, J. R., Clatworthy, M. R., Waldmann, H., Brewer, J. M., Okkenhaug, K., Cooke, A., Garside, P., and Wållberg, M.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Frontiers in Immunology
Publisher:Frontiers
ISSN:1664-3224
ISSN (Online):1664-3224
Copyright Holders:Copyright © 2018 Benson, Garcon, Recino, Ferdinand, Clatworthy, Waldmann, Brewer, Okkenhaug, Cooke, Garside and Wållberg
First Published:First published in Frontiers in Immunology 9: 1006
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
568541Defining the Role of Cell Migration in the Initiation and Regulation of Pathogenesis in Inflammatory ArthritisPaul GarsideArthritis Research UK (ARTRESUK)19788III -IMMUNOLOGY
602451Rheumatoid Arthritis Centre of Excellence (RACE - Towards a Cure)Iain McInnesArthritis Research UK (ARTRESUK)MP20298III -IMMUNOLOGY