Our immune system uses T cells to rapidly identify and respond to different kinds of pathogens, whether they're viruses or cancerous cells, for example. T cells have special abilities; naive T cells are on patrol through the body, searching for invaders that activate them, while memory T cells are poised to proliferate when a reinfection occurs. Both naive and memory T cells can stay in a quiescent state, a kind of dormancy in which the healthy function of the cell is preserved, but they are inactive, and stop dividing into daughter cells. Quiescence is necessary for T cells to maintain their function, and they will stay that way until something reawakens them. Researchers have now revealed more about how the quiescent state is maintained in T cells. The findings have been reported in Science.
This study has shown that a protein expressed in a subset of T cells, called CD8, is critical to quiescence. The researchers created a mouse model in which the expression of the CD8 protein could be carefully modulated. They found that when T cells which normally express CD8 no longer did, those T cells could not remain in a quiescent state.
"We may have to change how we teach T cell biology," said senior study author Lieping Chen, a professor at Yale University.
The work also indicated that another protein was involved; the PILRa protein, which is expressed on the surface of myeloid cells, interacts with CD8a to actively maintain quiescence. When the interaction between PILRa and CD8 was disrupted in human or mouse cells, both naive and CD8+ memory T cells were not able to enter a quiescent state, and the cells died. In a mouse model these cells left the animal susceptible to infection.
As people get older, they tend to have fewer naive and memory T cells, noted Chen. This makes us more vulnerable to infection as we get older. The study authors suggested that problems with quiescence may be related to this issue.
The researchers are hopeful that a better understanding of quiescence, such as why cells enter that state and how they remain there in good health, could help scientists improve immune dysfunction.