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

PLoS Pathogens

Vivien Béziat¹  Torbjörn Kjerstadius¹  Aukse Mickiene¹  Kim Blom¹  Jonas Klingström¹  Monika Braun¹  Lars Lindquist¹  Sara Gredmark-Russ¹  Nina Lagerqvist¹  Hans-Gustaf Ljunggren²  Jolita Pakalniene³  Laura Dailidyte³  Margit H. Lampen⁴  Jakob Michaëlsson⁵  Johan K. Sandberg⁶ 

[1] 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;Department of Infectious Diseases, Lithuanian University of Health Sciences, Kaunas, Lithuania;Human Genetics of Infectious Diseases Laboratory, Imagine Institute—INSERM U1163, Paris, France;Karolinska University Laboratory, Department of Clinical Microbiology, Karolinska University Hospital Solna, Stockholm, Sweden;Unit of Infectious Disease, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden

关键词: T cells;    Cytotoxic T cells;    Memory T cells;    Immune response;    Transcription factors;    Tick-borne encephalitis;    Blood;    Cerebrospinal fluid;   

DOI  :  10.1371/journal.ppat.1004622

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY