ArticleProceedings of the National Academy of Sciences of the United States of America2017
Visualizing context-dependent calcium signaling in encephalitogenic T cells in vivo by two-photon microscopy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Lack of junctional adhesion molecule (JAM)-B traps CD8 T cells in CNS border zones and ameliorates autoimmune neuroinflammation.Acta neuropathologica communications · 2025Article
- Life history of a brain autoreactive T cell: From thymus through intestine to blood-brain barrier and brain lesion.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Visualizing the activation of encephalitogenic T cells in the ileal lamina propria by in vivo two-photon imaging.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- CD4Science advances · 2023Article
- Contribution of Intravital Neuroimaging to Study Animal Models of Multiple Sclerosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- Review
- Autoimmunity in motion: Mechanisms of immune regulation and destruction revealed by in vivo imaging.Immunological reviews · 2022Review
- Skin and gut imprinted helper T cell subsets exhibit distinct functional phenotypes in central nervous system autoimmunity.Nature immunology · 2021Article
- Article
- Optimizing Calcium Detection Methods in Animal Systems: A Sandbox for Synthetic Biology.Biomolecules · 2021Review
- The contribution of thymic tolerance to central nervous system autoimmunity.Seminars in immunopathology · 2021Review
- Perivascular macrophages create an intravascular niche for CD8Clinical & translational immunology · 2021Article
- Oligodendrocyte myelin glycoprotein as a novel target for pathogenic autoimmunity in the CNS.Acta neuropathologica communications · 2020Article
- Seeing is believing: Visualizing immune cells and calcium signals at different stages of neuroinflammation.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Regulatory T cells suppress Th17 cell CaProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Dwellers and Trespassers: Mononuclear Phagocytes at the Borders of the Central Nervous System.Frontiers in immunology · 2020Review
- Imaging the dynamic interactions between immune cells and the neurovascular interface in the spinal cord.Experimental neurology · 2019Review
- LFA-1 Controls Th1 and Th17 Motility Behavior in the Inflamed Central Nervous System.Frontiers in immunology · 2019Article
- Small Molecule Antagonists of NAADP-Induced CaScientific reports · 2018Article
- Dominant role of microglial and macrophage innate immune responses in human ischemic infarcts.Brain pathology (Zurich, Switzerland) · 2018Article
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Authors and funding
15 authors.
Funding
Abstract
In experimental autoimmune encephalitis (EAE), autoimmune T cells are activated in the periphery before they home to the CNS. On their way, the T cells pass through a series of different cellular milieus where they receive signals that instruct them to invade their target tissues. These signals involve interaction with the surrounding stroma cells, in the presence or absence of autoantigens. To portray the serial signaling events, we studied a T-cell-mediated model of EAE combining in vivo two-photon microscopy with two different activation reporters, the FRET-based calcium biosensor Twitch1 and fluorescent NFAT. In vitro activated T cells first settle in secondary (2°) lymphatic tissues (e.g., the spleen) where, in the absence of autoantigen, they establish transient contacts with stroma cells as indicated by sporadic short-lived calcium spikes. The T cells then exit the spleen for the CNS where they first roll and crawl along the luminal surface of leptomeningeal vessels without showing calcium activity. Having crossed the blood-brain barrier, the T cells scan the leptomeningeal space for autoantigen-presenting cells (APCs). Sustained contacts result in long-lasting calcium activity and NFAT translocation, a measure of full T-cell activation. This process is sensitive to anti-MHC class II antibodies. Importantly, the capacity to activate T cells is not a general property of all leptomeningeal phagocytes, but varies between individual APCs. Our results identify distinct checkpoints of T-cell activation, controlling the capacity of myelin-specific T cells to invade and attack the CNS. These processes may be valuable therapeutic targets.
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