CD4^dimCD8^brightT cells are inversely associated with neuro-inflammatory markers among people with HIV

Objective:HIV-associated neuroinflammation persists in the brain despite suppressive combination antiretroviral therapy (cART). We evaluated associations between a subset of CD8⁺T cells, termed CD4^dimCD8^brightT cells, and soluble markers of immune activation and/or neuroinflammation in the cerebrospinal fluid (CSF) and plasma of people with HIV (PWH).Design:Fifteen cART-naive PWH were enrolled and underwent blood draw, lumbar puncture for CSF collection, and neuropsychological tests at week 0 (pre-cART) and 24 weeks after cART initiation.Methods:CSF and peripheral blood T cells were evaluated with flow cytometry and soluble markers of immune activation were measured by multiplex and singleplex assays. Spearman bootstrap correlation coefficients with 10 000 resamples were computed and reported with corresponding 95% confidence intervals (CIs) for each marker of interest and T-cell type.Results:The frequency of CSF CD4^dimCD8^brightT cells at week 0 was inversely related with CSF neopterin. In contrast, at week 24, CSF CD4^-CD8⁺T cells were positively correlated with CSF s100β, a marker of brain injury. In the blood, at week 0, CD4^dimCD8^brightT cells were inversely correlated with MCP-1, IP-10, IL-8, IL-6, G-CSF, and APRIL and positively correlated with plasma RANTES and MMP1. At week 0, the frequency of blood CD4^-CD8⁺were positively correlated with CRP and BAFF.Conclusion:CD4^dimCD8^brightT cells are associated with some anti-inflammatory properties, whereas CD4^-CD8⁺T cells may contribute to inflammation and injury. Assessing the contrast between these two cell populations in neuroHIV may inform targeted therapeutic intervention to reduce neuroinflammation and associated neurocognitive impairment.