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

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

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