Direct impact of T cells on neurons revealed by two-photon microscopy in living brain tissue.
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.
Nitsch
Robert
R
Institute of Anatomy, Department of Cell and Neurobiology, Humboldt University Medical School Charité, D-10098 Berlin, Germany.
Pohl
Elena E
EE
Smorodchenko
Alina
A
Infante-Duarte
Carmen
C
Aktas
Orhan
O
Zipp
Frauke
F
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002450:Cell Communication / Q000276:immunology / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D066298:In Vitro Techniques; D018942:Macrolides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors; D051379:Mice; D008815:Mice, Inbred Strains; D018991:Myelin Proteolipid Protein / Q000276:immunology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010047:Ovalbumin / Q000276:immunology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D018942:Macrolides; D008562:Membrane Glycoproteins; D018991:Myelin Proteolipid Protein; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; C036978:concanamycin A; D010047:Ovalbumin