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Immunity. 2007 Oct;27(4):670-84. Epub 2007 Oct 18.

Molecular signature of CD8+ T cell exhaustion during chronic viral infection.

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  • 1Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, 1510 Clifton Road Room G211, Atlanta, GA 30322, USA. jwherry@wistar.org

Erratum in

  • Immunity. 2007 Nov;27(5):824.

Abstract

Chronic viral infections often result in T cell exhaustion. To determine the molecular signature of exhaustion, we compared the gene-expression profiles of dysfunctional lymphocytic choriomeningitis virus (LCMV)-specific CD8(+) T cells from chronic infection to functional LCMV-specific effector and memory CD8(+) T cells generated after acute infection. These data showed that exhausted CD8(+) T cells: (1) overexpressed several inhibitory receptors, including PD-1, (2) had major changes in T cell receptor and cytokine signaling pathways, (3) displayed altered expression of genes involved in chemotaxis, adhesion, and migration, (4) expressed a distinct set of transcription factors, and (5) had profound metabolic and bioenergetic deficiencies. T cell exhaustion was progressive, and gene-expression profiling indicated that T cell exhaustion and anergy were distinct processes. Thus, functional exhaustion is probably due to both active suppression and passive defects in signaling and metabolism. These results provide a framework for designing rational immunotherapies during chronic infections.

PMID:
17950003
[PubMed - indexed for MEDLINE]
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