Teaching T cells
As any loyal Michigan alumnus can attest, the kind of education you get can make all the difference in the direction your life takes.
The same is true for cells in the immune system, says Cheong-Hee Chang.
“When you look at human beings, they are born, they have to be raised, and during the process, they have to be educated. It’s exactly the same concept for T cells, the immune cells that we study.”
Born in the thymus (a mass of glandular tissue located under your breastbone), T cells eventually grow up to fight invading microbes and other suspicious intruders—a crucial role in maintaining our health. In the course of their education, they have to learn two main things: to recognize infected cells and to kill only those cells, while leaving healthy cells alone.
If all goes right in the schooling process, T cells become successful, diligent workers when they graduate and join the labor force patrolling for and controlling infectious invaders. But if they’re not properly educated they may make serious blunders on the job such as attacking healthy cells, resulting in autoimmune diseases—rheumatoid arthritis, multiple sclerosis and lupus, for example. Or, they may ignore cells that should be destroyed, which is also detrimental to our well-being.
Chang’s lab studies how T cells behave, and then backtracks to figure out how the cells’ behavior relates to the type of education they received. The research group is particularly interested in a specific type of T cell called a CD4 T cell. Often mentioned in connection with HIV/AIDS, CD4 T cells are the cells that the HIV virus destroys, weakening patients’ immune systems. In fact, CD4 T cells are so important in controlling various aspects of immune reactions that serious health problems and eventually death result when these cells are defective or absent.
In humans, young CD4 T cells likely have two educational options. Normally, they are taught by epithelial cells in the thymus, but they also can engage in a sort of peer-tutoring, educating one another.
Research in Chang’s lab shows that “peer-educated” and epithelium-educated CD4 T cells function differently. One recent finding is that mice whose CD4 T cells were peer-educated are less prone to asthma-like airway inflammation than those whose T cells took the usual educational route, suggesting that people who have more self-educated T cells also may suffer less from asthma and allergies.
“It is possible, too, that these CD4 T cells contribute to development or control of other immune diseases,” says Chang.
Developing a mouse model for studying T cell alternative education was tricky, because mouse CD4 T cells normally follow only a single path: epithelium-based learning. But Chang’s group coaxed the cells into teaching one another, as their human equivalents sometimes do. While the mouse model will increase the researchers’ basic understanding of how CD4 T cells educated in different ways behave, the eventual goal is to compare those findings with observations of human CD4 T cells.
“Ultimately, we want to study peer-educated and epithelium-educated human CD4 T cells directly,” Chang says, “but to do that, we have to be able to distinguish between the two subsets of cells.…We need a marker—a sort of signature or fingerprint—to tell them apart. We don’t have that yet, but we’re working on finding one, and once we do, we’ll be able to compare human and mouse data and see whether the differences we’ve found correlate with any immune diseases.”
“Discovering such connections,” says Chang, “could be the key to finding preventive measures or cures for diseases that today can only be managed.”
