When T-cells Attack
Imagine not being able to tell the difference between good and bad, between healthy and unhealthy, between normal and infected. Now, imagine if this inability was fostered in a T-cell, whose sole purpose is to target and fight infections. The result? A variety of diseases that affect roughly five percent of our population.
“Rheumatoid arthritis, systemic lupus, and diabetes are illnesses where the lymphocytes [T-cells] have lost the ability to see the difference between the infection and the body’s own tissue,” says physician-scientist Dan Mueller, head of the Division of Rheumatic and Autoimmune Disease in the Department of Medicine at the Medical School.
Since coming to the U in 1992, Mueller has shaped the University’s autoimmunity program. Today, he spends much of his time in the lab researching different elements of T-cells.
Every T-cell has two receptors: an antigen receptor that watches for invaders such as micro-organisms, germs, or other pathogens and a co-stimulatory receptor that moves the T-cell to respond to the invader. So a T-cell’s antigen receptor alerts the cell and wakes it from its dormant state. Once the T-cell is activated, the co-stimulator receptor informs the T-cell of its next move. Typically, when the body’s own antigens are recognized, the activated T-cell will either revert back to its resting state or learn to tolerate the antigen. But a dangerous pathogen-derived antigen will cause T-cells to attack.
In patients with rheumatic and autoimmune diseases, however, the co-stimulatory receptor is impaired. Sometimes the T-cell will turn on its own body and attack healthy tissues; other times, it will ignore an infected site. Either way, when this happens, the targeted area will become inflamed, often leading to tissue damage and long-term disabilities.
As part of his research, Mueller is investigating the molecules in the co-stimulatory receptor’s signaling pathway that regulate and mount responses when the T-cell encounters an invader such as a pathogen or a perceived invader.
“If we can understand the biology of T-cell activation, we can develop therapeutic approaches that interfere with the signaling of the co-stimulatory receptor,” says Mueller, who currently works with animal models.
Unlike most immunosuppressive therapies which, once administered, will inhibit the function of many different T-cells (both damage-provoking and health-promoting), Mueller’s team focuses on developing a treatment that will isolate and target only dangerous T-cells. Mueller believes he can do this by controlling the functions of co-stimulatory receptors.
Though this research may seem technical, its impact one day will be extraordinary.
“Our current treatments for autoimmune disease often lack potency and can be complicated by infection,” says Mueller. “In the near future, we may be able to selectively control the signaling process for co-stimulatory receptors that cause the immune system to attack the body’s own tissues, without reducing the immune system’s response to harmful pathogens.”
--Emily Jensen
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