Asymmetric cell division plays an important role during the development of our nervous and digestive systems. It is thought that T cells, a type of immune cell, can also divide asymmetrically, giving rise to two different daughter cells. Now, St. Jude researchers have shown that the oncogene c-Myc can control this asymmetric division in T cells, which could potentially improve cancer therapy.
Douglas Green and his lab at St. Jude Children’s Research Hospital published their work earlier this week in the journal Nature.
Instead of producing two identical daughter cells, T cells can create two distinct daughter cells with different cell fates. One cell immediately responds to the infecting pathogen by generating effector T cells, while the other cell multiplies as memory T cells--representing a short- and long-term strategy for dealing with pathogens.
"Our study shows that the way in which the regulatory protein c-Myc distributes during asymmetric cell division directly influences the fate and roles of activated T cells," said Green in a news release. "We also show how this asymmetry is established and sustained."
The team showed that during asymmetric division of activated T cells, high levels of c-Myc group together in one daughter cell and not the other. A higher dose of c-Myc appeared to kick the daughter cell into action. They became effector T cells to fight the infection, while the daughter cell with a lower dose of c-Myc formed memory T cells, effectively coordinating an attack a month later if exposed to the same infecting pathogen.
They saw that effector T cells generated from a high c-Myc concentration had a positive feedback loop, enabling them to sustain high levels of c-Myc and maintain their effector T cell identity. When c-Myc in these cells was experimentally lowered the very switch of this protein abundance pushed these cells into becoming memory T cells instead.
"Our work suggests that it may be possible to manipulate the immune response by nudging production of c-Myc in one direction or the other," said Green. "Potentially that could mean more effective vaccines or help to advance T-cell immune therapy for cancer treatment."
Although it was known that T cells could undergo asymmetric cell division, this study was the first to show that T cells' behavior can be changed by manipulating their metabolic and regulatory pathways to produce different levels of c-Myc. Since c-Myc has been well characterized for its role in a wide range of cancers, this finding may lead to more effective vaccines and improved immunotherapies for cancer.