Abstract
Advancing age is associated with significant alterations in immune functions, including a decline in CD4 T cell function, in both mice and humans. In our previous report, we showed that CD4^+^CD25^–^ T cells in aged (24‐month‐old) mice, especially after in vitro pre‐stimulation of these cells, exhibit hyporesponsive and suppressive properties. We examined here whether the suppressive activity of aged CD4^+^CD25^–^ T cells is ascribable to a particular population within these cells. In vitro analyses revealed that cell populations rapidly extruding Rhodamine‐123 (R123) (referred to as R123^lo^ cells) in aged CD4^+^CD25^–^ T cells have a more potent suppressive function compared with R123^hi^ populations.In addition, CD103^+^ cells in freshly prepared aged CD4^+^CD25^–^R123^lo^ T cells had a most potent suppressive activity. Both R123^hi^ and R123^lo^ populations had individually stronger suppressive activity after pre‐stimulation than before pre‐stimulation. Furthermore, the R123^lo^ population in young CD4^+^CD25^–^ T cells also had different properties from R123^hi^ T cells: low responsiveness, no additive effect in proliferation assays, and the gain of a suppressive function after in vitro pre‐stimulation. Takentogether, these results suggest that CD4^+^CD25^–^R123^lo^ T cells are a unique population within whole CD4^+^CD25^–^ T cells. This population exists in the earlystage of the life span, and the properties in this population become obvious with aging, that is the gain of their suppressive activity.