High accumulation of T regulatory cells prevents the activation of immune responses in aged animals

In our previous in vivo study we demonstrated that young BALB/c mice effectively rejected the BM-185 tumor cells expressing enhanced GFP (EGFP) as a surrogate tumor Ag. In contrast, old BALB/c mice succumbed to the BM-185-EGFP tumors, indicating that there is a deficiency in old animals preventing the rejection of immunogenic tumors. There is cumulative evidence indicating that regulatory T (T-reg) cells control the activation of primary and memory T cell responses. However, very little is known about whether there is a relation between T-regs and the lack of immune responses in the aged. We evaluated young and aged animals, and our results demonstrated that there are significantly more CD4(+)CD25(+)FoxP3(+) and CD8(+)CD25(+)FoxP3(+) T-regs in the spleen and lymph nodes of old animals when compared with the young. Depletion of CD25(+) cells with anti-CD25 mAb induces the rejection of BM-185-EGFP cells, restores antitumor T cell cytotoxic activity, and results in the generation of a protective memory response against the BM-185 wild-type tumors in old mice. Furthermore, vaccination with CpG-oligode-oxynucleotide decreases the number of T-reg cells in old animals to the same levels as young mice, restoring the primary and memory antitumor immune responses against BM-185-EGFP tumors. Taken together, these results indicate that there is a direct correlation between the expansion of T-reg cells and immune deficiency in the old, and that depletion of these cells might be critical for restoring immune responses in aged animals.