Scientists at St. Jude Children’s Research Hospital have solved an immunology puzzle. A CD8+ T cell can have two functionally distinct daughter cells after it divides, despite the cells being genetically identical. The researchers have explained how, revealing one method the immune system uses to provide immediate and long-term protection. The research appears today in Molecular Cell.
The researchers showed how a specific protein complex guides translation of an important immune transcription factor in one region of the parent T cell. When the cell divides, because the transcription factor is only in one region, it is then inherited asymmetrically into two daughter cells. The transcription factor drives expression of a set of genes in one daughter cell, pushing it to become an effector cell, while the other becomes a memory cell.
“Our results hint that events that happen very early in a T cell’s life can influence the function of the cell much later,” said corresponding author Doug Green, Ph.D., St. Jude Department of Immunology chair. “We have uncovered one way in which the immune system ensures that when T cells are activated, the response will be diverse, with some cells, the effectors, launching a rapid assault on the invader and others hanging back in reserve for later, as memory cells.”
Two very different daughters with the same DNA
The immune system has many different cell types with varied functions. One major cell type is CD8+ T cells. These cells are responsible for directly killing infected and tumor cells. They are activated by a special cell that presents a bit of virus or tumor cell, called an antigen, on their surface. The point of contact between T cells and the antigen-presenting cells is called the immune synapse. After activation, the T cells divide into genetically identical daughter cells.
Many of the daughter cells become effector cells that also kill infected or cancer cells. However, some of the daughter cells become memory cells to help protect against future infections or the same cancer. Before this study, it was unclear how both effector and memory cells could come from the same parent T cell.
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