In rheumatoid arthritis-affected patients, an increase in the number of Foxp3-expressing CD4+CD28- T lymphocytes has been reported, and these senescent Treg cells expressed lower levels of CD25, showed higher SA-βgal activity, and produced higher levels of TNF-α, IFN-γ, and IL-17A, as compared with Foxp3+CD4+CD28+ lymphocytes [16]. This evidence concerns the gene CD28 and rheumatoid arthritis.