Deep phenotypic analysis of blood and lymphoid T and NK cells from HIV+ controllers and non-controllers

T and natural killer (NK) cells are important effector cells with key
roles in anti-HIV immunity, including in lymphoid tissues which is the
major site of HIV persistence. In this study, we used 42-parameter CyTOF
to conduct deep phenotyping of paired blood- and lymph node (LN)-derived T
and NK cells from three groups of HIV+ aviremic individuals: elite
controllers, and ART-suppressed individuals who had started therapy during
chronic vs. acute infection, that latter of which are associated with
improved treatment outcome. We found that acute-treated individuals are
enriched for specific subsets of T and NK cells, including blood-derived
CD56-CD16+ NK cells previously associated with HIV control, and LN-derived
CD4+ T follicular helper cells with heightened expansion potential. An
in-depth comparison of the features of the cells from blood vs. LN of
individuals from our cohort revealed that T cells from blood were more
activated than those from LNs. By contrast, LNs were enriched for
follicle-homing CXCR5+ CD8+ T cells, which expressed increased levels of
inhibitory receptors and markers of survival and proliferation as compared
to their CXCR5- counterparts. In addition, a subset of memory-like
CD56brightTCF1+ NK cells was enriched in LNs relative to blood. These
results together suggest unique T and NK cell features in acute-treated
individuals, and highlight the importance of examining effector cells not
only in blood but also the lymphoid tissue compartment where the reservoir
mostly persists, and where these cells take on distinct phenotypic
features.