How helper cells become killers to attack viruses and cancerous tumors
Researchers have discovered the mechanism that enables CD4 helper T cells to assume the more aggressive role of killer T cells in mounting an immune attack against viruses, cancerous tumors and other damaged or infected cells.
The finding could enable the development of more potent drugs for AIDS, cancer and many other diseases based on using this mechanism to trigger larger armies of killer T cells against infected or damaged cells.
The team led by the La Jolla Institute for Allergy 'n' Immunology conducted the study in collaboration with researchers from the RIKEN Institute in Japan.
CD4 helper T cells, which normally assist other cells of the immune system during an infection, and CD8 killer T cells, which directly attack and eliminate infected cells, are two of the body's most important immune cells for defending against diseases. Earlier research studies have shown that helper T cells can become killer cells in some instances. However, the specific mechanism of action that allowed this to occur was not known until now.
"We have identified the molecular switch that enables CD4 T cells to override their programming as helper cells and transform into cytolytic (killer) cells," said La Jolla Institute scientist and study co-leader Hilde Cheroutre, Ph.D.
"Our team also showed that these transformed helper T cells represent a separate and distinct population of cells. They are not a subset of TH-1 helper cells as previously thought," Cheroutre stated.
Jay A. Berzofsky, M.D., Ph.D., chief of the Vaccine Branch at the National Cancer Institute's Center for Cancer Research, called the finding "a major advance" that provides new understanding about the cell's lineage and basic mechanisms.
He added that the finding could also have important implications in cancer.
In the study, the researchers found that a certain transcription factor, which are molecules in the cell nucleus that control the activity of cells, continually suppresses the killer T cell lineage in helper T cells. Using mice, the team showed that turning off this transcription factor (ThPOK) enabled the helper cells in the body's peripheral areas, like the blood, spleen and the intestine, to override their original programming and to become killer T cells.
"While our work focused on the intestines, we found that helper T cells in all tissues of the body have the potential to become killer cells in response to recognition of viral, tumor or other antigens in the context of cytokines such as IL-15," said Dr. Cheroutre.
Dr. Cheroutre said she believes it may be possible, using the newly discovered mechanism, to turn the CD4 regulatory T cells into killer cells that would aid, rather than block, the immune system's attack on cancerous cells.
The findings were published in Nature Immunology.