In addition to repeated antigen stimuli, naturally occurring CD4+ CD25hi Foxp3+ TR cells and tumor-associated regulatory γδT-cells have been shown to induce a senescent phenotype on naïve and responder T-cells (Figure 1), characterized by down-regulation of CD27 and CD28 and expression of senescence-associated beta-galactosidase (SA-β-gal) [102,103]. This evidence concerns the gene CD4 and neoplasm.