Posted on September 13, 2004 at 9:26 a.m.
BIRMINGHAM, AL — Researchers at the University of Alabama at Birmingham (UAB) have created a protein shown to stop progression of a disease in mice that mimics multiple sclerosis (MS) in humans. Details of the study are published in the September 1 issue of the Journal of Immunology. “This research may have important implications for MS as well as other autoimmune diseases, such as lupus and leukemia,” said Chander Raman, Ph.D., assistant professor of medicine with UAB’s Division of Clinical Immunology/Rheumatology.
Approximately 400,000 Americans, primarily women, have MS, a neurological disease that affects the central nervous system. Individuals are affected differently, but symptoms may include fatigue, loss of balance and muscle coordination, slurred speech, tremors and stiffness.
Researchers discovered CD5, a molecule found on the surface of certain immune cells — T-cells and a small subset of B-cells — is responsible for the prolonged survival of these cells. “In patients with autoimmune diseases, activated immune cells persist,” Raman said. “The overabundance of these activated T-cell cells propagates disease as these cells target and destroy the body’s own healthy cells and tissues.”
The cell survival process is set in motion when CD5 is engaged by its ligand, a molecule that binds to CD5. This triggers the CD5 molecule to send cell survival signals. Researchers used soluble CD5, a synthetic molecule, to prevent the ligand binding to CD5. “This, in turn, prevents CD5 for signaling cell survival,” Raman said.
The study showed soluble CD5 is effective for short-term destruction of active immune T-cells. “This is very important,” Raman said. “Soluble CD5 acts to induce the death of all activated T-cells in the immune response. Long-term, this would not be desirable. However, in autoimmune diseases death of activated T-cells will promote recovery. Once we achieve the desired response, we can facilitate recovery of the immune system.”
This targeted approach to therapy offers a great advantage over broad-spectrum therapies that destroy all immune cells. “These therapies destroy both harmful immune cells as well as surrounding non-activated healthy lymphocytes,” Raman said. “This approach targets only those cells involved in disease progression.”
The 18-month study was supported in part by grants from the National Institutes of Health and the National Multiple Sclerosis Society. Other UAB researchers who collaborated on the study are Robert Axtell, microbiology graduate student; Scott Barnum, Ph.D., associate professor of microbiology; and Matthew Webb, Ph.D., biology graduate assistant.