Age-associated parallel increase of Foxp3+CD4+ regulatory and CD44+CD4+ memory T cells in SJL/J mice

Effector/memory T cells (Tem) are required to maintain successful immunity, while regulatory T cells (Treg) are required to prevent excessive/uncontrolled inflammation and/or autoimmunity. Although both Tem and Treg cells are increased during aging, the relationship between the increased proportion of Foxp3+ Treg cells and CD44+ Tem cells with aging is not clearly understood. We found in this report that Foxp3+ Treg cells are increased in parallel with CD44+ Tem cells in SJL/J mice with aging, and that all Foxp3+ Treg cells are of CD44+ Tem phenotype, suggesting that the increased Foxp3+ Treg cells originated from the expanded pool of CD44+ Tem cells with aging. Our in vitro kinetic studies further suggested that Foxp3+ Treg cells are converted through the CD44+ stage. Furthermore, we observed that although the balance between Foxp3+ Treg and CD44+Foxp3− Tem cells remained with aging, the aged mice have higher ratios of both Tem and Treg cells vs. naïve T cells resulting in the “shrunken” naïve T cell pools. Our results suggest that an age-associated imbalance of T cell repertoire is a mechanism that contributes to spontaneous occurrence of Hodgkin’s-like lymphoma in aged SJL/J mice.