Sept. 22, 2008

T Cells Provide Protection in ALS Mice

TUCSON, Sept. 22, 2008 - T cells, the foot soldiers of the immune system, are involved in protecting motor neurons (nerve cells that activate muscle) in ALS (amyotrophic lateral sclerosis, or Lou Gehrig's disease), a paralyzing neurologic disease, says a group of scientists led by MDA grantee Stanley Appel at Methodist Neurological Institute (MNI) in Houston.

Lead authors David R. Beers and Jenny S. Henkel, working with Appel at MNI,  published their findings online today in Proceedings of the National Academy of Sciences.

"Finding ways of protecting motor neurons is a major goal of our ALS research program," said Sharon Hesterlee, VP Translational Research at MDA. "As we gain a better understanding of the role of the immune system, we can leverage that knowledge for new therapeutic directions."

First, the researchers developed mice with a disease resembling human ALS that didn't have functional T cells and another group of mice with the same ALS-like disease but with functional T cells. They found that the mice without the T cells had an accelerated disease course and died earlier than the mice with T cells.

When the ALS mice lacking functional T cells were given an infusion of bone marrow stem cells, T cells appeared in their spinal cords, apparently from the infused stem cells. Their disease course slowed, and their survival was extended compared to the ALS mice without T cells.

The findings came as somewhat of a surprise, Appel says, since his team had expected that T cells would be toxic and not protective in the nervous system in ALS. Previous studies, some of which were conducted in his laboratory, had shown that other immune-system cells, called microglia, can cause dangerous inflammation in the central nervous system, the site of injury in this disease.

However, he notes, "It turns out that activated T cells can be a good thing in ALS. Instead of animals living longer with no T cells, they died in a shorter period of time."

The investigators zeroed in on "CD4-positive" T cells as the T-cell type that's likely conferring the benefit. "At least in this animal model, CD4 T cells are critical," Appel said. "T cells in general modulate the complex activities of the immune system, and our study demonstates that they can be neuroprotective." Appel added that T-cell therapy could be of value in human ALS, although further studies are needed.

"It's been known for some time that T cells are present at sites of injury in ALS patients as well as in mouse models of ALS," said investigator David Beers. "But until now, the role of these cells was unknown. This study demonstrates that T cells, through their interaction with other cells in the immune system, are protecting the cells in the spinal cord that cause muscle movement. It's now critically important to understand how T cells provide this neuroprotection."

Investigator Jenny Henkel noted, “We’re currently looking at a particular type of CD4 T cells that we think are providing this protection. These cells may eventually provide a readily accessible target for therapeutic intervention, not only for ALS but other neurodegenerative diseases."