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The Journal of Neuroscience, March 10, 2004, 24(10):2458-2464; doi:10.1523/JNEUROSCI.4703-03.2004

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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

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 sclerosis; neuronal cell death; neuroinflammation; calcium; glutamate; brain tissue; perforin

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Received Oct 17, 2003; revised January 6, 2004; accepted January 12, 2004.

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