CD151+ T cell accumulation as an indicator of premature immunological aging in People With HIV 3820

Description Despite effective antiviral therapy (ART), people with HIV (PWH) exhibit chronic immune hyperactivation, contributing to premature immunological aging (PIA) & early onset comorbidities. Cytotoxic CD4 + (cCD4) T cells, linked to persistent viral antigens, play a key role in inflammation & PIA. Previously, CD151 was identified as a marker for proinflammatory T cells. Here, we investigate if increased CD151+ T cell frequencies (%) contribute to PIA, & if high CD151+ T cell % at a young age indicate risk for comorbidities. Flow cytometry analyzed peripheral blood mononuclear cells (PBMCs) from HIV-negative (CTRL), PWH, & PWH that later developed a comorbidity (PWHc) for CD151, memory, & markers of activation & exhaustion. CD4+ & CD8+CD151+ T cell % increased with age in CTRL, while PWH showed accelerated accumulation. Younger PWHc displayed exceptionally high CD4+CD151+ T cell %, leading to an inverse correlation with age. CD4+CD151+ T cell % were higher in PWHc than in CTRL, with PWH trending higher. scRNA-seq further determined that increased CD151+ T cells in PWHc largely resulted from the accumulation of cytotoxic CD4+CD28–CD151+ & CD8+CD151+ effector memory CD45RA+ T cells. The early increase in proinflammatory CD151+ T cells in PWHc suggest a distinct PIA environment compared to the age-related trend in controls. By characterizing these T cell populations, we can gain insights into the mechanisms driving PIA & identify potential therapeutic targets to mitigate its impact. Funding Sources Funded in part by NIH grants R21-DA055490, R01-AI122842, R33-AI116188 and R33-AI133679. Parts of the work were performed in the UAB CFAR BSL2+ facilities and by the UAB CFAR Flow Cytometry Core, which are funded by NIH/NIAID P30-AI027767.