Visualizing the Autoimmune Process Underlying Diabetes | Imaris

Watching the Autoimmune Process Underlying Diabetes in Real Time


Dr. Ken Coppieters and Dr. Mathias von Herrath, La Jolla Institute for Allergy & Immunology

Researchers at the La Jolla Institute for Allergy & Immunology recently used intravital two-photon imaging and Imaris to create and analyze real-time movies of the cellular process underlying type 1 diabetes in mouse models. This new view provides insights into the autoimmune process that leads to type 1 diabetes and could influence future therapies.

Figure 1: This two-photon microscopy image shows part of a time series in which diabetogenic CD8 T cells (green), beta cells (magenta), and local vasculature (red) are seen in the pancreas.

Type 1 diabetes occurs when the body’s immune system destroys insulin-producing beta cells in the pancreas, but it has been challenging to image this process in action. The researchers performed intravital two-photon microscopy using a new procedure developed by Dr. Matthias von Herrath to surgically expose the pancreases of living mice.

“We were advised that Imaris is the best available software solution for automatic tracking and 4D visualization of image sequences captured by two-photon microscopy,” says the paper’s first author Dr. Ken Coppieters, who is formerly of the La Jolla Institute and now at Ghent University in Belgium.

The researchers first used Imaris for 3-D isosurfacing analysis of vascular perfusion patterns and vascular leakage. They found that control animals exhibited vascular integrity while the prediabetic animals had leaky vessels that allow T cells to move from the blood stream to the pancreas where they kill the beta cells.

They then conducted longitudinal 3-D tracking of T cells using Imaris. Measurements of the T cell velocity, directionality and arrest parameters revealed how these cells can launch an attack and in particular elucidated the time sequence of events during the destruction of beta cells within the pancreas of mice. The researchers found that the T cells move randomly throughout the pancreas until they encounter beta cells. They then slow down and release toxic substances that kill beta cells in a process that takes several hours. Imaris, Imaris Measurement Pro and Imaris Track were used to conduct this work.

The analysis also showed that it took tens of millions of T cells to produce massive beta cell destruction, a finding that provides evidence that the autoimmune attack is occurring for years before the disease is diagnosed. In humans, usually 90 percent of beta cells are destroyed before the disease produces enough symptoms to be recognized. “From a therapeutic perspective, these studies suggest that we may need to find a way to prevent the T cells from accessing the pancreas in the first place, since once they do, they have the ability to destroy several beta cells at a time,” Dr. Coppieters says.

T cells (purple dots) attack the pancreatic islets (green images in center), which contain the insulin-producing beta cells. The squiggly "tail" on the T cells, which switches from blue to red to yellow, is a tracking mechanism inserted by the researchers to record the T cell's velocity and attack time. Credit: Video by La Jolla Institute for Allergy & Immunology. Published by the Journal of Clinical Investigation.

Research Paper: Coppieters K, Amirian N, von Herrath M. Intravital imaging of CTLs killing islet cells in diabetic mice J Clin Invest. 2012 Jan 3;122(1):119-31. doi: 10.1172/JCI59285.

Multimedia Library
Application Images (3)
Publications Database
Caveolin-1 deficiency induces a MEK-ERK1/2-Snail-1-dependent epithelial–mesenchymal transition and fibrosis during peritoneal dialysis
The chemokine receptors ACKR2 and CCR2 reciprocally regulate lymphatic vessel density
Host DNA released in response to aluminum adjuvant enhances MHC class II-mediated antigen presentation and prolongs CD4 T-cell interactions with dendritic cells
Three-Dimensional Visualization of the Mouse Thymus Organization in Health and Immunodeficiency
Molecular and functional evidence of HCN4 and caveolin-3 interaction during cardiomyocyte differentiation from human embryonic stem cells
Shigella impairs T lymphocyte dynamics in vivo
Constitutive Lymphocyte Transmigration across the Basal Lamina of High Endothelial Venules Is Regulated by the Autotaxin/Lysophosphatidic Acid Axis
Sphingosine-1-phosphate-mediated osteoclast precursor monocyte migration is a critical point of control in antibone-resorptive action of active vitamin D
Opposing chemokine gradients control human thymocyte migration in situ
Motile invaded neutrophils in the small intestine of Toxoplasma gondii-infected mice reveal a potential mechanism for parasite spread
In vivo imaging of CD8+ T cell-mediated elimination of malaria liver stages
Chemokine Receptor CXCR6-Dependent Hepatic NK T Cell Accumulation Promotes Inflammation and Liver Fibrosis
Tetraspanin CD37 contributes to the initiation of cellular immunity by promoting dendritic cell migration
Perivascular Mast Cells Dynamically Probe Cutaneous Blood Vessels to Capture Immunoglobulin
Rgs13 Constrains Early B Cell Responses and Limits Germinal Center Sizes
Elimination of Self-Reactive T Cells in the Thymus: A Timeline for Negative Selection
NLRP10 is a NOD-like receptor essential to initiate adaptive immunity by dendritic cells
Expansion of Cortical and Medullary Sinuses Restrains Lymph Node Hypertrophy during Prolonged Inflammation
MT1-MMP regulates the PI3K (delta) Mi-2/NuRD-dependent control of macrophage immune function
Intravital imaging of CTLs killing islet cells in diabetic mice

Sign up for the Bitplane Newsletter!

Receive articles like this one, release notes, product launches, press releases and more with our regular newsletter. It's free to subscribe, will be sent every 6 weeks, and you can opt out at any time.


Try Imaris FREE for 10 days?