CD4 and viral infectious disease: 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).