期刊
FRONTIERS IN IMMUNOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2018.01006
关键词
type 1 diabetes; islets; multiphoton; imaging; immunotherapy; anti-CD3; T cell; autoimmunity
类别
资金
- NC3Rs [NC/M001083/1]
- Arthritis Research UK [19788, 20298]
- Diabetes UK [BDA 13/0004785]
- Diabetes Research and Wellness [SCA/OF/12/13]
- European Research Council 7th Frame Programme [health-f5-2009-241883]
- Wellcome Trust [095691/Z/11/Z]
- NIHR [NIHR-BRTU-10027]
- Cambridge University Isaac Newton trust
- BBSRC [BBS/E/B/000C0427, BBS/E/B/000C0407, BB/F015461/1, BBS/E/B/0000H329] Funding Source: UKRI
- Versus Arthritis [19788] Funding Source: researchfish
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.
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