Memory T cells have the critical job of remembering a first encounter with a foreign invader which enables the infection fighting cells to elicit a stronger and faster immune response the second time they meet the same attacker. Despite their importance, how memory T cells are generated has been poorly understood until now. A research team from The Scripps Research Institute has recently published a study in Immunity that investigates their origin.
The research team identified that a transcription factor, Runx3, initiates the transformation of dividing T cells into memory T cells. Since memory T cells are responsible for generating an immune response to vaccines, this new finding could lead to new drugs that could improve vaccine immune response. In addition, this deeper understand of memory T cells could improve treatments of chronic diseases such as cancer where T cells often produce a weaker response over time.
"There are instances such as chronic infection and tumors where the T cells differentiate in an aberrant way that shortens their life span and decreases their function," Matthew Pipkin, the study leader, says. "Because our study found that Runx3 is one of the earliest players during an immune response, manipulating it might be an avenue to basically turn back the clock and reprogram dysfunctional T cells into a format that is conducive to them developing into genuine memory cells that are protective.
The experiments showed that Runx3 has a key role in an initial immune response where T cells take action and differentiate into more specific cell types. Most of them become short-lived effector T cells but Runx3 determines that a subset of them become memory T cells which have a multiple-decade lifespan. Using RNA interference to inhibit Runx3 expression, the researchers found that there were much fewer precursor cells that develop into memory T cells. Cells with increased Runx3 produced more memory T cells and responded better after repeated infections with LCMV and Listeria monocytogenes. Additional experiments also showed that Runx3 acts very early on, within the first few hours of infection, to coordinate the differentiation of memory T cells.
The researchers plan to explore the development of a therapeutic that could increase Runx3 expression in cases where the protein is deficient. Also, they are working to identify other regulatory proteins that collaborate with Runx3.