The impact of CD8+ T-cell subsets on HIV replication in the cerebrospinal fluid

Objective: Central nervous system (CNS) involvement is common in human immunodeficiency virus (HIV) infection. We characterized T cell subsets in the cerebrospinal fluid (CSF) to determine the relationship between the local T cell repertoire and HIV load.

Methods: We analysed CSF and blood of 42 HIV-infected patients and 53 HIV-negative controls. Flow cytometry was used to determine T cell subsets and HIV PCR to quantify HIV RNA copy numbers in both compartments.

Results: HIV-positive patients had low CD4+/CD8+ T cell ratios in CSF and blood compared to control donors. HIV RNA copy numbers in CSF strongly correlated with CSF CD8+ T cell numbers, particularly in therapy-naïve, early-stage HIV-infected patients. Further characterization of CD8+ T cells in CSF revealed a shift from naïve CD8+ T cells to effector memory T cells (CD45RO+CD28-) in HIV-infected individuals. The presence of this population however was associated with high viral load while the appearance of effector T cells (CD45RA+CD28-) in CSF correlated with virus control.

Interpretation: We demonstrate the occurrence of a sequestered CD8+ T cell response to HIV in the CSF with a differential impact of CD8+ effector subsets on local viral burden.