Non-cytolytic control of HIV replication by CD8+ T cells

Replication of the human immunodeficiency virus (HIV) in CD4+ cells is suppressed in the presence of CD8+ cells from asymptomatic HIV-infected individuals. Although these CD8+ cells mediate HIV-specific, class I MHC restricted CTL activity, the predominant mechanism for inhibiting virus replication requires neither contact nor MHC matching between the CD8+ effector cells and CD4+ targets. Based on these data, a model involving two tiers of control on HIV replication by CD8+ cells is proposed. The first level would be mediated by a diffusible CD8+ cell-derived factor that prevents expression of the retroviral genome in a non-MHC restricted fashion. When this transcriptional control is lost, production of HIV proteins would sensitize the cell for lysis by class I MHC restricted, virus-specific CTL.