CD4 + T-cell–independent mechanisms suppress reactivation of latent tuberculosis in a macaque model of HIV coinfection

Significance According to the World Health Organization, one in three humans is latently infected withMycobacterium tuberculosis and 10% of these individuals risk developing active, clinical tuberculosis (TB) over their lifetimes. Coinfection with human immunodeficiency virus increases this risk substantially, with depletion of CD4+ T cells believed to drive disease progression. Although a minority of coinfected individuals can control the infection, the mechanisms underlying this phenomenon remain unknown. Modeling coinfection using macaques, we discovered that one-third of the animals maintained latency despite complete ablation of lung CD4+ T cells. We report that protective immune responses mediated by CD8+ T cells and B cells correlate with TB control. These findings have important implications in development of both prophylactic and therapeutic measures against TB and acquired immunodeficiency syndrome.