CD4 and viral infectious disease: Moreover, ex vivo studies have confirmed the existence of CD4+ T-cells with cytotoxic potential (CD4+ CTLs) in various human viral diseases such as cytomegalovirus (CMV), EBV, influenza, human immunodeficiency virus (HIV-1), dengue, Hantavirus, and parvovirus B19 [112,113,114], although the amount of peripheral CD4+ CTLs is usually very low in healthy individuals, and CD4+ CD28 null T-cells (subset of proinflammatory T-cells) are not predominantly present in synovial fluid [115].