# Alterations in Circulating T-Cell Subsets with Gut-Homing/Residency Phenotypes Associated with HIV-1 Status and Subclinical Atherosclerosis

## TL;DR

This study found that specific T-cell subsets with gut-homing traits are altered in HIV-positive individuals and linked to heart disease risk, even with antiretroviral therapy.

## Contribution

The study identifies novel T-cell phenotypes associated with HIV status and subclinical atherosclerosis in ART-treated individuals.

## Key findings

- Increased frequencies of CD8+TCRαβ+ and TCRγδ+ T-cells are associated with HIV status.
- CD4+ T-cells with specific gut-homing markers are elevated in HIV-positive individuals.
- Certain T-cell phenotypes correlate with subclinical atherosclerosis in HIV+ individuals.

## Abstract

Antiretroviral therapy (ART) controls HIV-1 replication in people with HIV-1 (PWH), but intestinal integrity impairment persists and fuels microbial translocation and chronic immune activation, thus heightening the cardiovascular disease (CVD) risk. Here, we sought to identify novel immunological correlates of the HIV and CVD status in ART-treated PWH (HIV+; n = 42) and uninfected participants (HIV−; n = 40) of the Canadian HIV and Aging Cohort Study (CHACS), with/without subclinical coronary atherosclerotic plaques, measured by Coronary Computed Tomography Angiography as total plaque volume (TPV, mm3). PBMCs were analyzed by flow cytometry for the expression of T-cell lineage (CD45, CD3, CD4, CD8αα, CD8αβ, TCRαβ, TCRγδ), epithelial cell (EpCAM/CD326), activation (HLA-DR), and gut-homing/residency markers (CD69, CD196/CCR6, CD199/CCR9, CD49d/Itgα4, CD103/ItgαE, Itgβ7). Alterations in the CD3+ T-cell pool, such as increased frequencies of CD8+TCRαβ+ and TCRγδ+ cells, to the detriment of CD4+TCRαβ+ subsets, were associated with the HIV status. Also, CD4+ T-cells with CD326+CD69+CCR6+ItgαE+ and CCR6+Itgβ7− phenotypes were increased in frequency in HIV+ vs. HIV− participants, together with a decreased frequency of CD8+ T-cells with an intraepithelial lymphocyte (IEL)-like CD3+CD4−TCRαβ+TCRγδ−CD8αα+CD8αβ− phenotype. Finally, multivariate logistic regression identified the frequency of ItgαE+CD8+, ItgαE−CD8+, CCR6+CD4+, and CCR6+Itgβ7−CD4+ T-cells as strong positive correlates of HIV status and atherosclerotic plaque in ART-treated PWH.