The disappearing CD4(+)T cells in HIV infection: a case of over-stimulation?

Infection with the human immunodeficiency virus (HIV) causes a gradual decline in essential immune-system cells called CD4(+)"helper" T cells. These cells are also principal viral targets, but, paradoxically, direct cell-killing does not explain their disappearance. HIV also induces a chronic and increasing state of immune activation. In a mathematical model of normal T-cell kinetics incorporating a cytokine growth factor, increased activation alone explains these T-cell losses, a switch from "naïve" to "memory" phenotype, and certain other features of HIV disease.