J Neurosci. 2004 Mar 10;24(10):2458-64
Nitsch R, Pohl EE, Smorodchenko A, Infante-Duarte C, Aktas O, Zipp
F.
Institute of Anatomy, Department of Cell and Neurobiology, Humboldt
University Medical School Charite, 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.