We first developed a 4-1BB-targeted optical probe, named IRDye-680RD-4-1BB mAb (monoclonal antibody), and evaluated its value for the detection of 4-1BB+ activated T cells in vivo as well as the diagnosis of rheumatoid arthritis (RA) in an adjuvant-induced arthritis (AIA) mouse model. This evidence concerns the gene TNFRSF9 and rheumatoid arthritis.