SNOWMASS, COLO. — The next generation of biological agents will be therapies that capitalize on the ability of regulatory T cells to keep the immune system in check, Randy Noelle, Ph.D., predicted at a symposium sponsored by the American College of Rheumatology.
First discovered 30 years ago, regulatory T-cell research was largely sidelined until interest in the field was renewed about 5 years ago, said Dr. Noelle, a professor of immunology at the Dartmouth-Hitchcock Medical Center, Lebanon, N.H.
“Over the past year, effective strategies have been developed to grow human regulatory T cells in vitro, and I would imagine that within a year you will see groups growing human regulatory T cells for reinfusion into patients for indications such as graft-versus-host disease,” he said.
“They will be the next wave of cell-based therapy that you will use to manage autoimmune disease,” Dr. Noelle told the audience of rheumatologists.
Regulatory T cells are the mechanism by which the body puts the brakes on the immune system functions of attack cells, or executor T cells, Dr. Noelle explained. Both regulatory T cells and executor T cells arise from CD4-positive cells. Research published last fall suggests that expression of the Lag-3 gene in CD4 cells differentiates them into regulatory T cells, which then limit the intensity of the autoimmune response (Immunity 2004;21:503-13).
Regulatory T cells represent about 5%-12% of an individual's CD4-positive T-cell population,
Although it is not known whether regulatory T cells suppress autoimmune activity directly or through cytokine expression, they have been shown to infiltrate tumors and attenuate the immune system response to them.
It has also been shown in mice that if mature, naive effector T cells are infused into immune-deficient mice, they develop inflammatory bowel disease. However, if regulatory T cells are infused at the same time, the mice remain healthy, Dr. Noelle said.
In addition, studies have demonstrated that T cells can prevent allergy and affect graft acceptance.
“I think they will have a resounding impact on our understanding of the development and pathogenesis of autoimmune diseases,” Dr. Noelle said.
Regulatory T cells suppress the functions of both CD4+ and CD8+ T cells. Dr. Randy Noelle