Researchers Identify Key Mechanism of Immune System
There is one class of diseases particularly intriguing to immunologists because it describes the body in revolt against itself. Autoimmune diseases result when the very cells meant to defend against foreign agents identify the body itself as foreign. Immune responses are mounted, and diseases such as multiple sclerosis, rheumatoid arthritis and insulin-dependent diabetes may develop. Now, HSPH researchers have cloned a protein that plays a key role in immune responses and could prove essential in controlling autoimmune diseases and other conditions. Their research was published in the March 17 issue of Cell.
Susanne
Szabo, research fellow in the Department of Immunology and Infectious
Diseases, Laurie Glimcher, Irene Heinz Given Professor of Immunology,
and their colleagues have identified and cloned a protein called T-bet
that controls the development of cells directly implicated in autoimmune
diseases.
A healthy immune system amounts to a delicate network of cell groups, each responsible for attacking different kinds of invasive bodies. One group, the T lymphocytes, serves as the bastion of the immune system. More than 10 years ago, researchers discovered that T lymphocytes could be divided into two subsets: Th1 and Th2 cells. But some factor must tell the immature T lymphocyte to turn into one of the two subsets, much like chromosomes tell a fertilized egg to develop into a male or female. T-bet, the protein cloned by the HSPH researchers and their colleagues, tells the lymphocyte to develop into Th1.
The balance of Th1 and Th2 cells in the bloodstream is crucial because these cells create compounds that can be harmful if overproduced. Asthma, for example, results when Th2 cells churn out too much interleukin-4.
Szabo had isolated T-bet in 1998, but had no idea what the protein did. She spent two years studying T-bet. When she discovered she had identified a fundamental component of the immune response, she described the feeling as extraordinary. "It was great because we experienced two years of frustration, and then the data jumped out at us," said Szabo.
Now that researchers have identified the protein directing the immature T lymphocyte into a Th1 cell, they may be able to manipulate the balance between the cell types from the beginning. But, more surprisingly, the researchers have discovered they can actually reverse the cell development and convert a Th1 cell into a Th2 cell. They can change the nature of the cell itself.
Glimcher's goal is to bring the newly found knowledge from bench to
bedside. She and her colleagues are working towards developing drug and
gene therapies that may help attack devastating diseases at cellular levels.
