The existence of unusual cytotoxic CD4+NKG2D+ T cells have been reported in individuals with chronic inflammatory diseases or viral infections [21, 22]; however, opposing evidence has implicated the existence of a normally-occurring CD4+NKG2D+ T cell population apparently endowed with regulatory activity in healthy individuals, and interestingly appeared to be inversely correlated with disease severity in patients with juvenile-onset systemic lupus erythematosus [23]. Here, CD4 is linked to viral infectious disease.