Establishing an evaluation system for T cell activation and anergy based on CD25 expression levels as an indicator

T cell anergy refers to a state where T cells become unresponsive, playing an important role in several types of immune tolerance, such as oral tolerance. This tolerance is vital for preventing some diseases, including food allergies. Understanding the mechanism underlying T cell anergy is essential to addressing food allergies. Previous studies often identified anergic T cells by their decreased ability to produce cytokine compared to the control cells. In the studies, unstimulated or naïve T cells were commonly used as the control cells. These systems could evaluate the hyporesponsiveness of anergic T cells; however, it was challenging to distinguish whether the decrease in cytokine production by anergic T cells was owing to anergy induction or merely a temporarily response to a certain stimulation. This complexity arises because some T cell responses are temporarily suppressed, even by activating stimuli. Therefore, this study aims to explore a new evaluation index that can differentiate the responsiveness of activated T cells from that of anergic T cells compared to the control cells. It was demonstrated that CD25 expression levels serve as an appropriate indicator for distinguishing between T-cell activation and anergy. Conversely, cytokine-producing ability proved inadequate for this purpose. It was found that CD25 expression increased in activated T cells than in naïve T cells, whereas it decreased in anergic T cells after restimulation. This occurred despite decreased cytokine production in the activated and anergic T cells than in the naïve T cells. This new evaluation system, centered on CD25 expression, may help in identifying the mechanism for determining T cell activation and anergy.