Initially considered as an in vitro artifact (2, 3), CD4+ CTL have been isolated in mice and humans in various pathologic conditions, including viral infections [human immunodeficiency virus (HIV) 1, influenza virus, cytomegalovirus (CMV), and Epstein–Barr virus (EBV)], autoimmune and autoinflammatory diseases (rheumatoid arthritis, ankylosing spondylitis), and malignancies (B cell chronic lymphocytic leukemia) (5–9, 26), as well as after vaccination (27, 28). This evidence concerns the gene CD4 and rheumatoid arthritis.