Compared with the normal group, CTLA-4 expression in CD4+ Foxp3+ cells in rheumatoid arthritis patients was reduced, which was associated with an increased rate of CTLA-4 internalization; artificially driving CTLA-4 to the T cell surface with PMA restored the suppressive function of the cells, but this restoration can be reversed by CTLA-4 inhibition (91). This evidence concerns the gene CD4 and rheumatoid arthritis.