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Studies show Tim-3 proteins key to immune responses

BOSTON -- The discovery that a protein present only on the surface of a select group of T-cells functions to inhibit aggressive immune responses could have important implications for organ transplant patients and patients with autoimmune diseases, and could prove equally relevant in the development of vaccines for the treatment of cancer, drug-resistant tuberculosis, HIV infections and other viral diseases. The findings from animal studies at Beth Israel Deaconess Medical Center (BIDMC) and Brigham and Women's Hospital (BWH) are described in two separate papers in the November 2003 issue of Nature Immunology.

Known as Tim-3 (T cell immunoglobulin domain, mucin domain), the proteins in question are found on the surface of TH1-helper type T cells, which when activated become the body's first line of defense against foreign microbes.

"Activated TH1-type helper T cells both participate in and help orchestrate the attack on cells bearing proteins, thereby guarding against infection," explains Terry Strom, MD, Chief of Immunology at BIDMC and Professor of Medicine at Harvard Medical School. "Nature gave us these cells as a critical defense against microbes."

However, he adds, these same T-cell responses must always be carefully balanced -- left unchecked, they can become overly aggressive, leading to inflammatory tissue injury and resultant autoimmune diseases, including diabetes, rheumatoid arthritis and inflammatory bowel disease. Similar problems develop among transplant patients when T-cells mount unnecessary defenses against their new organs, leading to organ rejection.

The two Nature Immunology papers, by senior authors Strom and BWH immunologist Vijay Kuchroo, DVM, PhD, found, for the first time, that Tim-3 proteins selectively serve as "checkpoints" for the immune system, helping to keep activated TH1 T-cell responses under control. Kuchroo is Associate Professor of Neurology at Harvard Medical School.

"Knowing that these proteins are
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Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
30-Oct-2003


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