March 16, 2004
Boston Cure Project
A group of German scientists seeking to understand the role of T cells in MS and similar diseases have discovered that direct contact with T cells can cause neurons to die. Using new imaging technology, they observed interactions between neurons and T cells in living brain tissue, and found that T cell contact causes neurons to undergo oscillations in their calcium uptake, leading to an overload of calcium, and death.
To carry out this experiment, the scientists extracted brain tissue from mice and put slices of tissue in a thermoregulated chamber with oxygenated artificial cerebral spinal fluid to keep it alive. Then they added activated T cells to the surface of the tissue. T cells were labeled with red fluorescent dye and the tissue was labeled with a green calcium indicator dye, so that T cells and neuronal calcium uptake could be observed via two-photon microscopy. The scientists were able to capture sequential images of the T cells at varying depths within the tissue, and observed the behavior of the cells infiltrating the tissue and coming into contact with neurons. They were also able to observe the neurons' calcium uptake oscillations and overload after contact with T cells. They found two strategies for preventing the calcium oscillations and overload, which were blocking release of perforin by T cells and blocking glutamate receptors on the neurons.
There are a number of reasons why this experiment is interesting. This
is the first study to analyze T-cell/neuron interactions and dynamics in
living brain tissue. Whereas other studies have only looked at preserved
brain tissue on slides or used simple cell cultures, this study explores
how T cells can damage neurons in their actual networked environment. Also,
its focus on collateral T cell-induced damage to neurons is very relevant
to MS, in which the importance of axonal damage is increasingly becoming
recognized. Future experiments using this type of setup may help in the
development of neuroprotective therapies to prevent neuronal death in MS
and other diseases.
Copyright © 2004, Boston Cure Project