CTLA-4 expression on VZV-specific T cells in CSF and blood is specifically increased in patients with VZV related central nervous system infections

Background

: VZV-reactivation may lead to symptomatic central nervous system (CNS) diseases, but identification of VZV as causative pathogen of CNS-diseases is challenging. This study was performed to characterize VZV-specific T-cells from cerebrospinal fluid (CSF) and blood of patients with active CNS-disease and to determine whether this may improve differential diagnosis.

Methods

: 27 patients with pleocytosis in the CSF were recruited and classified into three groups (10 VZV-related, 10 non-VZV-related, 7 unclear). VZV-specific CD4⁺ T-cells were quantified in CSF and blood after simultaneous stimulation with a VZV-antigen-lysate and detection of cytokines (IFNγ, IL-2, TNFα) and CTLA-4. Polyclonal stimulation served as positive control.

Results

: VZV-specific CD4⁺ T-cell-frequencies were highest in both CSF (p = 0.0001) and blood (p = 0.011) of patients with VZV-infection, and were enriched at the site of infection (p = 0.002). While cytokine expression-profiles only showed minor differences between the groups, CTLA-4 expression-levels on VZV-specific T-cells from CSF and blood were significantly increased in VZV-related CNS-infections (p = 0.0002 and p<0.0001) and clearly identified VZV-related CNS-diseases (100% sensitivity and 100% specificity). Polyclonally stimulated T-cells did not show any quantitative and phenotypical differences between the groups.

Conclusions

: Increased frequency and CTLA-4 expression of VZV-specific T-cells from CSF or blood are specifically found in patients with VZV-related CNS-infection.

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