Jigsaw falling into place: A review and perspective of lymphoid tissue CD8+ T cells and control of HIV.

•While blood CD8+ T cells control HIV using cytolytic functions, lymphoid tissue CD8+ T cells do so via non-cytolytic functions•HIV-specific CD8+ T cells in lymphoid and mucosal tissues are largely tissue-resident memory cells•The frequency of follicular CD8+ T cells negatively correlates with HIV viral load•Expression of inhibitory receptors by CD8+ T cells in lymphoid tissues do not necessarily indicate exhaustion•Lessons from autoimmune diseases suggest that a cure strategy inducing cytotoxic CD8+ T cells might cause undesired pathology