Specificity and Dynamics of Effector and Memory CD8 T Cell Responses in Human Tick-Borne Encephalitis Virus Infection

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. © 2015 blom et al.