Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

J. Neurosci. 24 (10): 2458-2464

Copyright © 2004 by the Society for Neuroscience.


Cellular/Molecular

Direct Impact of T Cells on Neurons Revealed by Two-Photon Microscopy in Living Brain Tissue

Robert Nitsch,1 * Elena E. Pohl,1 * Alina Smorodchenko,2 Carmen Infante-Duarte,2 Orhan Aktas,2 , and Frauke Zipp2

Institutes of 1Anatomy, Department of Cell and Neurobiology, and 2Neuroimmunology, Humboldt University Medical School Charité, D-10098 Berlin, Germany

Abstract: Encephalitogenic T cells invade the brain during neuroinflammation such as multiple sclerosis (MS), inducing damage to myelin sheaths and oligodendrocytes. Only recently, neuronal structures were reported to be a crucial target in the disease. Here, two-photon microscopy using ion-sensitive dyes revealed that within the complex cellular network of living brain tissue, proteolipid protein (PLP)-specific T cells and T cells recognizing the nonmurine antigen ovalbumin (OVA) directly and independently of the major histocompatibility complex (MHC) contact neurons in which they induce calcium oscillations. T cell contact finally resulted in a lethal increase in neuronal calcium levels. This could be prevented by blocking both perforin and glutamate receptors. For the first time, our data provide direct insight into the activity of T cells in the living brain and their detrimental impact on neurons.

Key Words: multiple sclerosisneuronal cell deathneuroinflammationcalciumglutamatebrain tissueperforin


Received for publication Oct 17, 2003. Revision received January 6, 2004. Accepted for publication January 12, 2004.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Two-Photon Imaging of Immune Cells in Neural Tissue.
R. Niesner, V. Siffrin, and F. Zipp (2013)
Cold Spring Harb Protoc 2013, pdb.prot073528
   Abstract »    Full Text »    PDF »
Narcolepsy: autoimmunity, effector T cell activation due to infection, or T cell independent, major histocompatibility complex class II induced neuronal loss?.
A. Fontana, H. Gast, W. Reith, M. Recher, T. Birchler, and C. L. Bassetti (2010)
Brain 133, 1300-1311
   Abstract »    Full Text »    PDF »
Cytotoxic CD8+ T Cell-Neuron Interactions: Perforin-Dependent Electrical Silencing Precedes But Is Not Causally Linked to Neuronal Cell Death.
S. G. Meuth, A. M. Herrmann, O. J. Simon, V. Siffrin, N. Melzer, S. Bittner, P. Meuth, H. F. Langer, S. Hallermann, N. Boldakowa, et al. (2009)
J. Neurosci. 29, 15397-15409
   Abstract »    Full Text »    PDF »
CD8+ T cells and neuronal damage: direct and collateral mechanisms of cytotoxicity and impaired electrical excitability.
N. Melzer, S. G. Meuth, and H. Wiendl (2009)
FASEB J 23, 3659-3673
   Abstract »    Full Text »    PDF »
Protection from fatal viral encephalomyelitis: AMPA receptor antagonists have a direct effect on the inflammatory response to infection.
I. P. Greene, E.-Y. Lee, N. Prow, B. Ngwang, and D. E. Griffin (2008)
PNAS 105, 3575-3580
   Abstract »    Full Text »    PDF »
Geranylgeranylation but Not GTP Loading Determines Rho Migratory Function in T Cells.
S. Waiczies, I. Bendix, T. Prozorovski, M. Ratner, I. Nazarenko, C. F. Pfueller, A. U. Brandt, J. Herz, S. Brocke, O. Ullrich, et al. (2007)
J. Immunol. 179, 6024-6032
   Abstract »    Full Text »    PDF »
Death Ligands and Autoimmune Demyelination.
O. Aktas, T. Prozorovski, and F. Zipp (2006)
Neuroscientist 12, 305-316
   Abstract »    PDF »
Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research.
R. Gold, C. Linington, and H. Lassmann (2006)
Brain 129, 1953-1971
   Abstract »    Full Text »    PDF »
CD8+ lymphocyte-mediated injury of dorsal root ganglion neurons during lentivirus infection: CD154-dependent cell contact neurotoxicity..
Y. Zhu, J. Antony, S. Liu, J. A. Martinez, F. Giuliani, D. Zochodne, and C. Power (2006)
J. Neurosci. 26, 3396-3403
   Abstract »    Full Text »    PDF »
Abeta-induced meningoencephalitis is IFN-{gamma}-dependent and is associated with T cell-dependent clearance of Abeta in a mouse model of Alzheimer's disease.
A. Monsonego, J. Imitola, S. Petrovic, V. Zota, A. Nemirovsky, R. Baron, Y. Fisher, T. Owens, and H. L. Weiner (2006)
PNAS 103, 5048-5053
   Abstract »    Full Text »    PDF »
Traumatic Injury and the Presence of Antigen Differentially Contribute to T-Cell Recruitment in the CNS.
C. Ling, M. Sandor, M. Suresh, and Z. Fabry (2006)
J. Neurosci. 26, 731-741
   Abstract »    Full Text »    PDF »
Hyperphosphorylation and Aggregation of Tau in Experimental Autoimmune Encephalomyelitis.
A. Schneider, G. W. Araujo, K. Trajkovic, M. M. Herrmann, D. Merkler, E.-M. Mandelkow, R. Weissert, and M. Simons (2004)
J. Biol. Chem. 279, 55833-55839
   Abstract »    Full Text »    PDF »
The Neuroscientist Comments.
(2004)
Neuroscientist 10, 275-276
   PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882