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Rare Immune Cell Involved in Multiple Sclerosis

A unique type of immune cell may contribute to multiple sclerosis (MS), researchers report. The discovery helps explain the effects of one of the newest experimental therapies for MS and could lead to improved treatments for MS and related disorders.

MS is an autoimmune disease in which the body's own immune system attacks the brain and spinal cord, resulting in nerve damage. Nearly 400,000 people in the U.S. are affected by the disease. Symptoms include problems with coordination and balance, muscle weakness, numbness or tingling, vision loss and slurred speech. In the worst cases, MS can cause partial or complete paralysis.

In 2007, NIH-funded researchers implicated the interleukin 2 (IL-2) receptor in MS. One function of IL-2 is to mobilize immune system T cells to expand and attack. The drug daclizumab blocks the IL-2 receptor. Ongoing clinical trials have shown that it helps quiet the autoimmune response in MS patients.

When daclizumab was first tested against MS, researchers theorized that it was acting directly on T cells, shutting off their IL-2 receptors. However, the IL-2 receptor is found on several types of immune cells. The drug's precise effects on the legions of cells that make up the immune system aren't well understood.

Recent work from a team led by Dr. Bibiana Bielekova of NIH's National Institute of Neurological Disorders and Stroke (NINDS) revealed that daclizumab's effects on T cells are mostly indirect. They found that the drug also affects cells of the innate immune system—the rapid, blunt first line of defense against infection. One such effect is to stimulate cells called natural killer cells.

In their new study, Bielekova's team investigated levels of innate immune cells in people taking daclizumab. The researchers obtained blood samples from daclizumab-treated MS patients, untreated MS patients and healthy subjects. They then isolated innate immune cells for classification. Their results appeared on August 1, 2012, in Science Translational Medicine.

The scientists found that MS patients had higher levels of an innate immune cell called lymphoid tissue inducer (LTi) than did healthy subjects. LTi cells direct lymph node development during early life, but their role during adulthood isn't clear. In MS patients receiving daclizumab, the number of LTi cells was lower than in those who weren't taking the drug. Daclizumab appears to steer the body away from producing LTi cells in favor of producing natural killer cells.

Patients receiving daclizumab also had reduced signs of inflammation in the cerebrospinal fluid that surrounds the brain. The finding provides an indirect link between LTi cells and brain inflammation in MS.

This study is the first to link LTi cells to an autoimmune disease. “While further study is required to confirm the role of LTi cells in autoimmunity, our results point to the cells as a promising target for the development of new drugs to treat autoimmune disorders,” says Bielekova.