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

S Sharma, AL Dominguez… - The Journal of Immunology, 2006 - journals.aai.org
S Sharma, AL Dominguez, J Lustgarten
The Journal of Immunology, 2006journals.aai.org
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 …
Abstract
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-oligodeoxynucleotide 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.
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