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How does the immune system fight off threats to the brain? New research yields fresh insight
Date:4/30/2012

y release seem to cause a reaction in many neighboring, uninfected cells suggesting a very open connection. These latter studies question the role of immunological synapses.

Using a unique live-cell imaging technique developed by the team, the new results show that the gasket connection focuses the T cell attack on the infected cell, but is leaky. This creates a two-tier response when a killer T cell goes after an infection.

"The T cell targets the infected cell preferentially, but it also secretes cytokines that reach a number of other cells in the neighborhood," says Lowenstein. "The immunological synapse fails to restrict how far cytokines can spread."

The research team, including U-M postdoctoral fellow Nicholas Sanderson, Ph.D., made the finding using a live-cell imaging method they developed that allows them to detect how many cells are exposed to the cytokine interferon gamma.

While the immunological synapse "gasket" ensured that the targeted cell was hit first by cytokines, other cells in the area soon showed signs of having received the same cytokine signal.

What's more, the researchers confirmed that the killer T cell carried out its killer function only on the targeted, infected cell it had attached to sparing nearby cells.

"This work disproves the idea that T cells secrete cytokines indiscriminately in the brain, but shows that T cell cytokine secretion affects a larger area beyond the targeted cell," says Lowenstein. "This helps settle the quandary of why widespread response to cytokines are seen, even when immune cells form specific immunological synapses only with target cells."

The finding, he adds, will help illuminate at a molecular level how the brain gets rid of infection. But it also hints at how the body's own T cells might mount the misguided attack on normal healthy brain cells in autoimmune diseases. The findings clarify how widespread effects can be obtained in spite of v
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Contact: Kara Gavin
kegavin@umich.edu
734-764-2220
University of Michigan Health System
Source:Eurekalert  

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