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Chapter 9: Immunology of TBEV infection

Even though the antibody response during memory cells mostly found in non-lymphoid
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TBE has been studied to some extent, the organs.
cellular aspects of B cell response, including
phenotype and activation status, as well as the T cell activation and phenotype during TBE
overall B cell role in TBE pathogenesis remain
to be investigated. T cell activation and phenotype was
investigated longitudinally in TBE patients
during the second phase of the disease, from
T lymphocyte responses during TBE
the time of hospitalization up to the
T cells are characterized by the expression of convalescent period. Peripheral blood T cells
the cell surface marker CD3, which forms a were found to be activated (as determined by

complex with the T cell specific receptors. Ki67 and CD38 co-expression), with the
Conventionally, the T cells are divided into two activation peaking at one week after
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groups with different immune functions: T hospitalization (Figure 2). In contrast to CD8
helper (CD4) and cytotoxic (CD8) cells, based T cells, CD4 T cells showed only low levels of
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on their surface expression of either CD4 or activation at this time of infection. Activated
CD8 markers. Activated CD4 T cells secrete CD8 T cells had increased expression of
various cytokines that orchestrate the perforin and granzyme B and passed through
immune response by activating B cells, CD8 T an effector phase prior to differentiation into
cells, macrophages and other cells of the memory cells. TBEV-specific CD8 T cells were
immune system. CD4 cells are restricted to further shown to be mainly monofunctional in
recognizing peptides presented on MHC class response to TBEV-peptide stimulation early
II molecules on APCs, whereas the CD8 cells after hospitalization, but became more
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recognize peptides presented on MHC class I polyfunctional in the convalescent phase.
molecules. CD8 T cells have a cytolytic ability Additionally, TBEV-specific CD8 T cells express
to kill infected host cells. The killing is higher levels of α4- and β1-integrins than the
mediated by the release of cytolytic proteins bulk CD8 T cells, which may indicate their
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like perforin and granzyme. Most CD8 T cells ability to migrate into the CNS.
are also efficient cytokine producers. These data indicate that the primary CD8 T cell
Adequate T cell responses, both CD4 and CD8, response to TBEV infection occurs during the
are important during viral infections. The second phase of TBE, as the peak of activation
effector CD8 T cells contribute to the of CD8 T cells along with the occurrence of
clearance of the infection and provide long- TBEV-specific CD8 T cells take place at about
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lasting immunity. CD4 T cells have a central one week into the second phase of TBE. In
“helper” role to assist and activate B cells and a yellow fever vaccine-based infectious model
CD8 T cells. After the naïve T cells encounter the peak of CD8 T cell response was observed
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an antigen they differentiate into effector T at day 15 after immunization. This may
cells, with the majority of the effector cells suggest a slight delay of CD8 T cell activation
dying off after clearance of the infection, with during TBEV infection as compared to the
only a small pool of cells remaining as memory yellow fever vaccine-based infectious model.
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cells. Memory cells can respond rapidly upon However, without access to patient samples
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re-exposure to the same infectious agent. during the first phase of TBE it is difficult to
Different subsets of memory cells can be explain the exact kinetics of T cell responses.
defined based on their phenotypic markers,
with the central memory cells homing to

secondary lymphoid organs and effector

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