Format

Send to

Choose Destination
PLoS Pathog. 2015 Jan 22;11(1):e1004622. doi: 10.1371/journal.ppat.1004622. eCollection 2015 Jan.

Specificity and dynamics of effector and memory CD8 T cell responses in human tick-borne encephalitis virus infection.

Author information

1
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
2
Department of Infectious Diseases, Lithuanian University of Health Sciences, Kaunas, Lithuania.
3
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; Human Genetics of Infectious Diseases Laboratory, Imagine Institute-INSERM U1163, Paris, France.
4
Karolinska University Laboratory, Department of Clinical Microbiology, Karolinska University Hospital Solna, Stockholm, Sweden.
5
Department of Infectious Diseases, Karolinska University Hospital Huddinge, Stockholm, Sweden; Unit of Infectious Disease, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
6
Department of Infectious Diseases, Lithuanian University of Health Sciences, Kaunas, Lithuania; Unit of Infectious Disease, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
7
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Infectious Diseases, Karolinska University Hospital Huddinge, Stockholm, Sweden.

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.

PMID:
25611738
PMCID:
PMC4303297
DOI:
10.1371/journal.ppat.1004622
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center