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

Immunity. 2007 Oct;27(4):670-84. doi: 10.1016/j.immuni.2007.09.006. Epub 2007 Oct 18.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Chronic Disease
  • Clonal Anergy
  • Female
  • Flow Cytometry
  • Gene Expression / immunology*
  • Gene Expression Profiling
  • Immunologic Memory / genetics*
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Virus Diseases / immunology*

Associated data

  • GEO/GSM235537
  • GEO/GSM235538
  • GEO/GSM235539
  • GEO/GSM235540
  • GEO/GSM235541
  • GEO/GSM235542
  • GEO/GSM235543
  • GEO/GSM235544
  • GEO/GSM235545
  • GEO/GSM235546
  • GEO/GSM235547
  • GEO/GSM235548
  • GEO/GSM235549
  • GEO/GSM235550
  • GEO/GSM235551