Background:
Atherosclerotic cardiovascular disease (ASCVD) is one of the leading causes of morbidity and mortality in people living with HIV (PLHIV). Understanding the association between circulating immune cells and carotid plaque presence in PLHIV holds the potential to identify novel immunological mechanisms driving plaque progression in PLHIV. Flow cytometry, allows identification and quantification of immune cells within heterogeneous populations.
Methods:
Our study analyzed data from the 2000HIV study (NCT03994835), comprising 1188 individuals with valid carotid ultrasound, without previous ASCVD and with valid high-dimensional flow cytometry measurements. This Dutch multi-center cross-sectional study focuses on virally suppressed PLHIV and is divided into a discovery cohort (n= 989) and validation cohort (n= 194). High dimensional flow cytometry was performed to identify the major blood immune cell subsets (403 populations) and their functional status. We performed linear regression models adjusted for age, sex and seasonality. Findings from the discovery cohort after correction for multiple testing were validated in the validation cohort.
Results:
In total 584 participants (49.2%) had a carotid plaque. Our findings revealed higher numbers of different CD8+ T cell subsets in individuals with carotid plaques (figure 1) both in the discovery and validation cohort. Among these CD8+ T cell subsets, increased proportions of T cell effector memory cells expressing CCR4, CCR6, CXCR3 and CXCR5 were observed (FDR < 0.05 for discovery and p < 0.05 in validation cohort). Furthermore, absolute numbers of CD8+ Tc1 cells expressing the exhaustion marker PD1, were increased in those with carotid plaques as compared with individuals without carotid plaques.
Conclusions:
In this comprehensive study in PLHIV under suppressive ART, we identified differences within CD8+ T cell populations in individuals with carotid plaques. These alterations span activated and exhausted cell phenotypes. Our findings underscore a role of CD8+ T cells in atherogenesis. Furthermore, the concurrent elevation of CD8+ Tc1 cells expressing the exhaustion marker PD1 provides further insight into the dynamic interplay of immune responses in atherosclerosis.
