PLoS Pathogens | |
Specificity and Dynamics of Effector and Memory CD8 T Cell Responses in Human Tick-Borne Encephalitis Virus Infection | |
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
【 预 览 】
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