Back to Search
Start Over
Molecular signature of CD8+ T cell exhaustion during chronic viral infection.
- Source :
-
Immunity [Immunity] 2007 Oct; Vol. 27 (4), pp. 670-84. Date of Electronic Publication: 2007 Oct 18. - Publication Year :
- 2007
-
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.
- Subjects :
- Animals
CD8-Positive T-Lymphocytes cytology
Cell Differentiation immunology
Chronic Disease
Clonal Anergy
Female
Flow Cytometry
Gene Expression Profiling
Lymphocyte Activation genetics
Lymphocyte Activation immunology
Lymphocytic choriomeningitis virus immunology
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Oligonucleotide Array Sequence Analysis
Phenotype
CD8-Positive T-Lymphocytes immunology
Gene Expression immunology
Immunologic Memory genetics
Virus Diseases immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1074-7613
- Volume :
- 27
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Immunity
- Publication Type :
- Academic Journal
- Accession number :
- 17950003
- Full Text :
- https://doi.org/10.1016/j.immuni.2007.09.006