Messaging the Immune System

By Troy Goodman

The powerful immune system protein IL-21 acts as a molecular go-between to help the body's infection-fighting CD4 and CD8 T cells accomplish their missions.

It’s true of any defensive force, from the military to microbiology: Communication is key to coordinating a successful attack on invaders. A recent breakthrough by UAB researchers could help improve that cross-talk among cells, giving the body’s natural defenses a fighting chance against deadly chronic infections like human immunodeficiency virus (HIV) and hepatitis C, says Allan Zajac, Ph.D., an associate professor in UAB’s Department of Microbiology.

Previously, scientists had been at a loss to explain how two different T cells worked in tandem—the CD4 T cells that help the immune system know when to attack (“helper T cells”) and the CD8 T cells that do the actual virus killing (“killer T cells”). Any successful communication between the two would require a good messenger molecule; in a study published in the journal Science, Zajac and his UAB lab report that messenger is the powerful immune system protein interleukin-21 (IL-21).

IL-21 is a molecule made by CD4 T cells, Zajac explains. “And one of the hallmarks of HIV infection, for example, is that your CD4 T cells go away. So they cannot make the normal array of helper molecules. After identifying IL-21, we gave it to mice that lacked CD4 T cells, and it improved their immune responses. If we add IL-21 to a human immune response, the results might be similarly impressive.”

The human body already makes IL-21, Zajac notes, but its levels may be insufficient under certain circumstances. IL-21 is thought to have a lot of beneficial effects, including helping T cell and antibody responses, Zajac says. He also suggests that IL-21 may be the missing link that keeps T cells from becoming exhausted or depleted during the long battle against a chronic invader like HIV. But he adds that better understanding of IL-21 comes with a caution—this powerful protein may have its own side effects, beyond infection problems, that would require physician monitoring.

Zajac says that research teams outside Alabama have looked at IL-21 responses in cancer biology, for example, with positive results. Seattle-based ZymoGenetics Inc., which is testing a commercially viable IL-21 agent unrelated to UAB, reports that the molecule likely could serve as an immunity booster when administered with chemotherapy or as a single-agent cancer killer.

Further IL-21 research is moving forward at UAB. Zajac has proposed a study that would restore IL-21 to normal levels in a model of HIV infection to see if it boosts the body’s antiviral attack.

This article originally appeared in UAB Medicine, the magazine of the UAB School of Medicine.