CD4 and HIV infectious disease: While the acute CD4 depletion observed in the initial phase of HIV infection is likely due to direct cytopathic effects of the virus, the mechanism/s underlying the steady decline of the CD4 T cell pool during the chronic phase of infection are unclear and are felt to be associated with “immune activation.” We hypothesized that the combination of two distinct forces: homeostatic (CD4 T cell depletion) and inflammatory (HIV-driven IFN-α), lead to a form of T cell activation that results in a decline in the CD4 T cell pool and an increase in the CD8 T cells.