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LIAI Scientists Make Important Finding on Regulation of Immune Cell Memory

Posted on: Thursday, 3 March 2005, 06:00 CST

Researchers at the La Jolla Institute for Allergy & Immunology have added a significant milestone to scientific understanding of the molecular mechanisms that trigger immune cell memory. The finding could lead to future advancements in treatments for cancer, AIDS and autoimmune diseases as well as enhanced vaccine development.

In a paper, "CD4+ T-cell help regulates CD8+ T-cell memory via TRAIL-mediated activation-induced cell death," published today in the scientific journal Nature, Stephen Schoenberger, Ph.D., and a team of scientists analyzed T cells, which are disease-fighting cells of the body's immune system that are responsible for recognizing foreign invaders and tumors. They sought to identify molecular differences that cause some responding T cells to become immune "memory" cells while other molecular changes cause most responding T cells to subsequently die. Memory cells are so named because they are long-lived and remember dangerous microbes or tumors. Memory cells are extremely important for immune function because they fight recurring infections, and the generation of immune memory is the basis for successful vaccination.

The scientists found that the protein TRAIL plays a key role in derailing the T cells' development into memory cells. The La Jolla Institute researchers have also taken a major step forward in understanding why the successful interaction of the two major T cell types -- killer T cells, which recognize and destroy cancerous or infected cells -- and helper T cells, which assist in activating immune responses, is critical for the killer T cells to develop into immune memory cells. In earlier findings, Dr. Schoenberger and his team had shown that helper T cells enable killer T cells to survive when they re-encounter infected cells. When this process goes smoothly, the killer T cells multiply, attack and destroy the infected cells. "But if there is no help (from the helper T cells) when the killer T cells are first activated, then the next time the killer T cells see the tumor or virus, they start killing themselves," explained Edith Janssen, Ph.D., first author on the study. "They do this by making the TRAIL protein, which induces cell suicide."

Dr. Schoenberger notes that the finding opens up the possibility of creating therapeutic interventions for many illnesses. "It (the TRAIL protein) is a substance that they (the killer T cells) make," he said. "Knowing this provides a window of opportunity to block the action of TRAIL and rescue the T cell, thereby allowing its recruitment into beneficial immune response." Dr. Schoenberger's team was able to successfully block the TRAIL protein in controlled laboratory studies of mice.

Mitchell Kronenberg, Ph.D., LIAI President and Scientific Director, said the research is regarded as very exciting by the scientific community. "This finding offers medical science the potential to one day control and regulate T cell response," he said. "T cells are important for protecting us from infectious pathogens. They also play an important role in autoimmune disease, where T cells mistakenly attack normal body tissues. Scientists may be able to devise treatments that will instigate, rather than block the TRAIL protein, in order to kill off threatening cells."

About LIAI

Founded in 1988, the La Jolla Institute for Allergy and Immunology is a non-profit medical research center dedicated to increasing knowledge and improving human health through studies of the immune system. Researchers at the institute carry out studies designed to understand and lead to the development of cures for cancer, allergy and asthma, infectious diseases, and autoimmune diseases such as diabetes, inflammatory bowel disease and arthritis. The institute's research staff includes over 100 Ph.Ds.

Source: Business Wire

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