Defining a functionally distinct subset of human memory CD4+ T cells that are CD25POS and FOXP3NEG

Surface expression of the IL-2 receptor a-chain (CD25) has been used to discriminate between CD4+CD25HIFOXP3+ regulatory T (Treg) cells and CD4+CD25NEGFOXP3- non-Treg cells. However, this study reports that the majority of resting human memory CD4+FOXP3- T cells expresses intermediate levels of CD25 and that CD25 expression can be used to delineate a functionally distinct memory subpopulation. The CD25NEG memory T-cell population contains the vast majority of late differentiated cells that respond to antigens associated with chronic immune responses and are increased in patients with systemic lupus erythematosus (SLE). In contrast, the CD25INT memory T cells respond to antigens associated with recall responses, produce a greater array of cytokines, and are less dependent on costimulation for effector responses due to their expression of CD25. Lastly, compared to the CD25NEG and Treg-cell populations, the CD25INT memory population is lost to a greater degree from the blood of cancer patients treated with IL-2. Collectively, these results show that in humans, a large proportion of CD4+ memory T cells express intermediate levels of CD25, and this CD25INTFOXP3- subset is a functionally distinct memory population that is uniquely affected by IL-2.