Journal of acquired immune deficiency syndromes (1999) 2017 02 07() doi 10.1097/QAI.0000000000001301
Central nervous system (CNS) infiltration by CD8+ T cells is associated with neuroinflammation in many neurodegenerative diseases, including HIV-associated dementia. However, the role of CD8+ T cells in the CNS during acute HIV infection is unknown.
We analyzed the phenotype, gene expression, TCR repertoire and HIV-specificity of CD8+ T cells in cerebrospinal fluid (CSF) of a unique cohort captured during the earliest stages of acute HIV infection (AHI) (n=26), chronic (n=23), and uninfected (n=8).
CSF CD8+ T cells were elevated in AHI compared to uninfected controls. The frequency of activated CSF CD8+ T cells positively correlated to CSF HIV RNA and to markers of CNS inflammation. In contrast, activated CSF CD8+ T cells during chronic infection (CHI) were associated with markers of neurological injury and microglial activation. CSF CD8+ T cells in AHI exhibited increased functional gene expression profiles associated with CD8+ T cells effector function, proliferation and TCR signaling, a unique restricted TCR Vbeta repertoire and contained HIV-specific CD8+ T cells directed to unique HIV epitopes compared to the periphery.
These results suggest that CSF CD8+ T cells in AHI expanding in the CNS are functional and directed against HIV antigens. These cells could thus play a beneficial role protective of injury seen in CHI if cART is initiated early.