Functional outcomes of platelet NK cell complexes in people living with HIV 3193

Description Anti-retroviral therapy effectively suppresses HIV replication but does not restore NK cell function in people with HIV (PWH). The mechanism behind NK dysfunction is unclear, though increased platelet-immune cell complex formation has been observed in PWH. We hypothesize that platelet-NK cell complexes (PNKCs) play a role in NK dysfunction during HIV infection. To investigate, we analyzed PBMCs from both people without HIV (PWOH) and PWH, as well as in vitro platelet-NK co-cultures, using flow cytometry and correlative light and electron microscopy to identify NK cell phenotypes and functions. In Rhesus macaques (RMs), treatment with inclacumab (INC) was given before and after SIV infection, and NK cell phenotypes and functions were monitored. We found increased PNKC levels in PWH, regardless of NK subset, sex, or age. PNKCs displayed higher CD314 and CD25 expression than non-PNKCs, and NK cells co-cultured with activated platelets exhibited enhanced cytotoxicity. In RMs, INC altered NK phenotypes and reduced their effector functions. This study identifies elevated PNKCs in PWH with altered phenotypes. Platelet-NK interactions lead to NK activation and cytotoxicity, potentially leading to NK dysfunction over time. These findings may inform future therapeutic strategies where platelet inhibitors could reduce chronic NK activation. Funding Sources NIH/NIAID: T32 AI158105, P30 AI117970, R01 NS126090, R01 NS131063 Topic Categories Immune Mechanisms of Human Disease (HUM)