Immune Quiescence Model of protection from HIV infection. (A) In HIV-susceptible individuals, infection is established in resting and activated CD4+ target cells. Inflammation drives infiltration of activated target cells, which fuel viral propagation and dissemination of infection. (B) In HESN, elevated levels of Tregs maintain low levels of T cell activation, leading to reduced availability of activated CD4+ target cells. HIV establishes infection in resting T cells, which support low levels of virus replication. Reduced expression of proinflammatory cytokines and chemokines prevents infiltration of activated target cells. Productive infection is therefore reduced in HESN, allowing HIV-specific CTL sufficient opportunity to clear the low-level infection and prevent dissemination.