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


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.

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@article{Wherry2007MolecularSO, title={Molecular signature of CD8+ T cell exhaustion during chronic viral infection.}, author={Elaine Wherry and Sang-Jun Ha and Susan M Kaech and W. Nicholas Haining and Surojit Sarkar and Vandana Kalia and Shruti Subramaniam and Joseph N Blattman and Daniel L. Barber and Rafi Ahmed}, journal={Immunity}, year={2007}, volume={27 4}, pages={670-84} }