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 CD8+ T cells are crucial for immunity against viral infections, including HIV. Several characteristics of CD8+ T cells, such as polyfunctionality and cytotoxicity, have been correlated with effective control of HIV. However, most of these correlates have been established in the peripheral blood. Meanwhile, HIV primarily replicates in lymphoid tissues. Therefore, it is unclear which aspects of CD8+ T cell biology are shared and which are different between blood and lymphoid tissues in the context of HIV infection. In this review, we will recapitulate the latest advancements of our knowledge on lymphoid tissue CD8+ T cells during HIV infection and discuss the insights these advancements might provide for the development of a HIV cure. [ABSTRACT FROM AUTHOR]