Aregay et al. Poor virus-specific T-cell response early after tick-borne encephalitis virus infection. Emerg Microbes Infect. 2024; 13(1): 2317909. doi:10.1080/22221751.2024.2317909

Outcomes of TBE virus infections vary widely from asymptomatic infection to severe disease with neurological sequelae and even with fatal outcome.

Factors that underlie disease manifestations and severity are poorly understood. It has been suggested that cell-mediated immune response contributes to protection against infection.

Therefore, the magnitude, specificity and functional properties of TBE virus specific T-cells and antibody response was analyzed in a cohort of TBE patients with either meningoencephalitis (70%), meningoencephalomyelitis (16.7%) and meningitis (13.3%).

The frequency of early T-cell response to the structural proteins C and E and to non-structural proteins NS1 and NS5 inversely correlated with disease severity, e.g. the frequency of IFN-γ producing T-cells specific for E, NS1 and NS5 were significant lower in patients with meningoencephalomyelitis than in patients with meningitis. Thus, poor T-cell response may be the cause or the consequence of more severe clinical course of acute TBE illness.

The frequency of INF-γ + CD4+ T-cells specific for C and E were significantly lower in patients with meningoencephalomyelitis which was in concordance with results obtained in the ELISpot assay. The frequency of IFN-γ+ CD8+ T-cells directed to NS1, NS3 and NS5 were significantly higher in patients with meningitis than in patients with meningoencephalomyelitis.

Consistent with the significantly higher E-, NS1- and NS5-specific T-cell responses observed in patients with relatively mild forms of TBE, patients with strongest E, NS1 and NS5-specific T-cell responses early after diagnosis of TBE, also had a favorable long-term outcome without neurological sequelae.

No correlation was found for early antibody response to various structural and non-structural protein domains with disease outcome.

The authors concluded that a poor T-cell response upon TBE virus infection is the cause of more severe disease and clinical manifestation.

TBE Book