CD25 Levels on T Cells Determine Whether They Become Effector or Memory Cells

Scientists at Emory Vaccine Center are providing new insights into the role of interleukin 2 signaling on the differentiation of T cells into long-lived memory cells as a result of an acute infection. They conclude that their results uphold previous, contradictory hypotheses suggesting that IL-2 can have both positive and negative effects on CD8⁺ memory T cell development.

The results are published in Immunity in a paper titled “Prolonged Interleukin-2Rα Expression on Virus-Specific CD8⁺ T Cells Favors Terminal-Effector Differentiation In Vivo.”

The team, led by the vaccine center’s director, Rafi Ahmed, Ph.D., followed the kinetics of CD25 expression on T cells in mice infected with lymphocytic choriomeningitis virus; CD25 is the alpha chain of the IL-2 receptor. They then determined the fate of CD8⁺ T cells expressing differential levels of CD25. 

They found that while all CD8⁺ T cells upregulated the expression of CD25 similarly as an immediate response to infection, after a few days the T cells could essentially be separated into two groups, one displaying high levels of CD25, and the other low levels of CD25. It was the low-level CD25 T cells that appeared to differentiate into functional long-lived memory cells. These cells were less sensitive to IL2.

Conversely, T cells expressing high levels of CD25 and exposed to prolonged IL2 signals proliferated more rapidly into effector cells and were far shorter-lived. Interestingly, when mice were given extra IL2, the T cells exhibited more pronounced effector characteristics. As the infection began to clear, all the T cells subsequently reduced their levels of CD25 expression until there was no evidence of any difference in levels of the molecule.

“Apparently, cells that receive prolonged IL-2 signals are pushed further down the effector path and hence exhibit decreased potential to form long-lived memory cells,” comments co-author Surojit Sarker, Ph.D. “It may be beneficial that not all of the T cells burn themselves out fighting the virus so that memory-fated cells can conserve resources for the next encounter.”

The authors suggest their observations combined with previous findings by other researchers, suggest that too little as well as too much IL2 can be detrimental to the development of immunological memory.