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Published on: March 1, 2017
In vivo imaging in autoimmune diseases in the central nervous system
1Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig-Maximilians Universitaet Muenchen, Munich, Germany; Neuroimmunology Group, Max-Planck Institute of Neurobiology, Martinsried, Germany.
Insights
Intravital imaging visualizes autoreactive T cell infiltration into the central nervous system (CNS). This technique tracks T cells
Area of Science:
- Neuroimmunology
- Cellular Biology
- Medical Imaging
Background:
- Intravital imaging allows direct in vivo observation of cellular motility and function, contrasting with in vitro and traditional in vivo analyses.
- Autoreactive T cell infiltration into the central nervous system (CNS) is crucial in autoimmune diseases.
- Understanding T cell interactions and activation within the CNS is vital for developing targeted therapies.
Purpose of the Study:
- To review recent intravital imaging studies focusing on autoreactive T cell infiltration into the CNS.
- To provide technical background on the methods used for visualizing T cell behavior in vivo.
- To highlight the role of intravital imaging in understanding T cell activation and its therapeutic potential.
Main Methods:
- Summarizing recent literature on intravital imaging of T cell CNS infiltration.
- Describing the migratory pathways and cellular interactions of autoreactive T cells.
- Utilizing protein-based sensors to visualize T cell activation in vivo, including calcium signaling and NFAT translocation.
Main Results:
- Autoreactive T cells interact with endothelial cells and splenocytes to gain migratory phenotypes.
- T cells cross the blood-brain barrier via leptomeningeal vessels or choroid plexus.
- In vivo visualization confirmed T cell activation through antigen recognition, marked by calcium influx and NFAT nuclear translocation.
Conclusions:
- Intravital imaging provides unprecedented insights into the dynamic behavior of autoreactive T cells within the CNS.
- This technique visualizes key steps in T cell activation, including antigen recognition and signaling.
- Intravital imaging serves as a powerful platform for developing and testing novel therapeutic strategies for CNS autoimmune diseases.
Abstract:
Intravital imaging is becoming more popular and is being used to visualize cellular motility and functions. In contrast to in vitro analysis, which resembles in vivo analysis, intravital imaging can be used to observe and analyze cells directly in vivo. In this review, I will summarize recent imaging studies of autoreactive T cell infiltration into the central nervous system (CNS) and provide technical background. During their in vivo journey, autoreactive T cells interact with many different cells. At first, autoreactive T cells interact with endothelial cells in the airways of the lung or with splenocytes, where they acquire a migratory phenotype to infiltrate into the CNS. After arriving at the CNS, they interact with endothelial cells of the leptomeningeal vessels or the choroid plexus before passing through the blood-brain barrier. CNS-infiltrating T cells become activated by recognizing endogenous autoantigens presented by local antigen-presenting cells (APCs). This activation was visualized in vivo by using protein-based sensors. One such sensor detects changes in intracellular calcium concentration as an early marker of T cell activation. Another sensor detects translocation of Nuclear factor of activated T-cells (NFAT) from cytosol to nucleus as a definitive sign of T cell activation. Importantly, intravital imaging is not just used to visualize cellular behavior. Together with precise analysis, intravital imaging deepens our knowledge of cellular functions in living organs and also provides a platform for developing therapeutic treatments.
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