Journal
JOURNAL OF NEUROSCIENCE
Volume 24, Issue 10, Pages 2458-2464Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4703-03.2004
Keywords
multiple sclerosis; neuronal cell death; neuroinflammation; calcium; glutamate; brain tissue; perforin
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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.
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