Abstract
T and natural killer (NK) cells are effector cells with key roles in anti-HIV immunity, including in lymphoid tissues, the major site of HIV persistence. However, little is known about the features of these effector cells from people living with HIV (PLWH), particularly from those who initiated antiretroviral therapy (ART) during acute infection. Our study design was to use 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 (N = 5), and ART-suppressed individuals who had started therapy during chronic (N = 6) vs. acute infection (N = 8), the latter of which is associated with better outcomes. 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. LNs 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.
Highlights
Lymphocytes with cytotoxic capabilities, including both T and natural killer (NK) cells, are important effectors that play crucial roles in controlling infections by pathogenic viruses, including HIV
To characterize T and NK cells from aviremic People living with HIV (PLWH), we recruited 13 HIV+ participants who donated both PBMCs and lymph node (LN) aspirates during the same study visit, along with an additional 6 participants who donated PBMCs alone (Table S1)
As expected [19], TCF1 expression levels to be highest in the CD56bright subset in blood, and further demonstrated that this was true in the LN compartment as well (Figure 5E)
Summary
Lymphocytes with cytotoxic capabilities, including both T and natural killer (NK) cells, are important effectors that play crucial roles in controlling infections by pathogenic viruses, including HIV. PLWH who initiate ART during acute infection have lower levels of T cell activation [37] and a smaller HIV reservoir that decays more rapidly [38, 39], relative to those who initiated treatment during chronic infection This is likely due to better preserved immune responses in these individuals [40,41,42,43]. A better understanding of the features of effector cells from PLWH who initiated ART during acute infection may provide insights into the basis of a better-preserved anti-HIV immune response and post-treatment control of HIV. Overall, these observations suggest different ways in which HIV-infected people achieve full or partial immunological control of their infection. By comparing across participant groups (elite controllers, acutely-treated HIV+ ART-suppressed individuals, and chronically-treated HIV+ ART-suppressed individuals), and between sampling sites (blood and LN), we define characteristics of T and NK cells that associate with a specific state of HIV control, and identify profound phenotypic differences between effector cells from blood and lymphoid tissue
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