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Human CD8+ T-cell differentiation in response to viruses

Nature Reviews Immunology volume 3, pages 931–939 (2003)Cite this article

Key Points

  • Most markers that define functional subsets of CD8+ T cells are regulated by activation, which complicates their use as differentiation markers.

  • Although during acute infection overall similarities dominate between T cells specific for different viruses, their phenotypes seem to be distinct in the memory/latency stage.

  • Infection with cytomegalovirus has a dominant influence on the circulating CD8+ T-cell pool, promoting the generation and maintenance of a population with stable cytolytic function.

  • Specific co-stimulatory ligands (or cytokines) present during the initial priming or memory/latency stages might direct CD8+ T-cell differentiation and account for differences between T cells that react to different viruses.

Abstract

CD8+ T cells are essential in the defence against viruses. Recently, peptide–HLA class I tetramers have been used to study immune responses to viruses in humans. This approach has indicated consecutive stages of human CD8+ T-cell development in acute viral infection and has illustrated the heterogeneity of CD8+ T cells that are specific for latent viruses. Here, we summarize these findings and discuss their significance for our understanding of antigen-induced CD8+ T-cell maturation in humans.

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Figure 1: Graph showing the T-cell response to infection with virus.
Figure 2: Phenotypic changes of virus-specific T cells from acute infection to the latent state.
Figure 3: A branched model for human CD8+ T-cell development.

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Acknowledgements

We thank Dr E. Eldering for helpful discussions.

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Authors and Affiliations

  1. Department of Experimental Immunology, Academic Medical Centre, P.O. Box 11600, Amsterdam, 1100AZ, The Netherlands

    René A. W. van Lier & Laila E. Gamadia

  2. Renal Transplant Unit and Division of Rheumatology and Clinical Immunology, Academic Medical Centre, P.O. Box 11600, Amsterdam, 1100AZ, The Netherlands

    Ineke J. M. ten Berge & Laila E. Gamadia

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  1. René A. W. van Lier
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DATABASES

LocusLink

2B4

CCL21

CCR5

CCR7

CD11A

CD27

CD28

CD38

CD56

CD57

CD62L

CD70

IFN-γ

IL-2

IL-4

IL-5

Entrez

CMV

EBV

HBV

HCV

HIV

LCMV

VZV

Glossary

PERFORIN

A calcium-sensitive membraneolytic protein that is found in cytoplasmic granules of cytotoxic T lymphocytes and natural killer cells.

GRANZYME B

A member of a family of serine proteinases that are mainly found in the cytoplasmic granules of cytotoxic T lymphocytes and natural killer cells.

MHC CLASS I TETRAMERS

Fluorescent-labelled tetravalent complexes of MHC class I or class II molecules complexed with antigenic peptide. They can be used to identify antigen-specific T cells by flow cytometry.

SEROPOSITIVITY

The presence of virus-specific antibodies in the serum of an individual.

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van Lier, R., ten Berge, I. & Gamadia, L. Human CD8+ T-cell differentiation in response to viruses. Nat Rev Immunol 3, 931–939 (2003). https://doi.org/10.1038/nri1254

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