Abstract
Tick-borne encephalitis virus (TBEV) is transferred to humans by ticks. The virus causes tick-borne encephalitis (TBE) with symptoms such as meningitis and meningoencephalitis. About one third of the patients suffer from long-lasting sequelae after clearance of the infection. Studies of the immune response during TBEV-infection are essential to the understanding of host responses to TBEV-infection and for the development of therapeutics. Here, we studied in detail the primary CD8 T cell response to TBEV in patients with acute TBE. Peripheral blood CD8 T cells mounted a considerable response to TBEV-infection as assessed by Ki67 and CD38 co-expression. These activated cells showed a CD45RA-CCR7-CD127- phenotype at day 7 after hospitalization, phenotypically defining them as effector cells. An immunodominant HLA-A2-restricted TBEV epitope was identified and utilized to study the characteristics and temporal dynamics of the antigen-specific response. The functional profile of TBEV-specific CD8 T cells was dominated by variants of mono-functional cells as the effector response matured. Antigen-specific CD8 T cells predominantly displayed a distinct Eomes+Ki67+T-bet+ effector phenotype at the peak of the response, which transitioned to an Eomes-Ki67-T-bet+ phenotype as the infection resolved and memory was established. These transcription factors thus characterize and discriminate stages of the antigen-specific T cell response during acute TBEV-infection. Altogether, CD8 T cells responded strongly to acute TBEV infection and passed through an effector phase, prior to gradual differentiation into memory cells with distinct transcription factor expression-patterns throughout the different phases.
Highlights
Tick-borne encephalitis virus (TBEV) is a single-stranded flavivirus and the causative agent of tick-borne encephalitis (TBE)
We studied the primary T cell-mediated immune response in patients diagnosed with TBEV infection
We show that CD8 T cells mount a vigorous TBEV-specific response within one week of hospitalization
Summary
Tick-borne encephalitis virus (TBEV) is a single-stranded flavivirus and the causative agent of tick-borne encephalitis (TBE). TBEV is transferred to humans from infected Ixodes ticks. TBE is an increasing public health problem occuring throughout northern and central Europe and Asia, with thousands of encephalitis cases reported annually despite available TBE vaccines [1, 2]. Epidemiological studies suggest that around 25% of all infected individuals develop clinical disease [3, 4]. TBE has a characteristic biphasic course with influenza-like illness followed by a second neuroinvasive phase with neurological symptoms of variable severity, ranging from meningitis to severe meningoencephalitis. About a third of the patients eventually suffer from long-term sequelae including neuropsychiatric problems, headaches, and a substantial decrease in quality of life (reviewed in [5])
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