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Impaired NFAT nuclear translocation results in split exhaustion of virus-specific CD8+ T cell functions during chronic viral infection.

ABSTRACT: In persistent viral infections, the host's immune system is challenged by the constant exposure to antigen, potentially causing continuous activation of CD8(+) T cells with subsequent immunopathology. Here we demonstrate, for experimental chronic lymphocytic choriomeningitis virus and human HIV infection, that upon prolonged in vivo exposure to antigen, TCR-triggered Ca(2+) flux, degranulation, and cytotoxicity are maintained on a cellular level, whereas cytokine production is severely impaired because of a selective defect in activation-induced NFAT nuclear translocation. During chronic infection, this differential regulation of pathways leading to diverse effector functions may allow CD8(+) T cells to sustain some degree of local viral control by direct cytotoxicity while limiting systemic immune pathology by silencing cytokine production.

SUBMITTER: Agnellini P

PROVIDER: S-EPMC1815473 | biostudies-literature |

REPOSITORIES: biostudies-literature

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The transcription factor NFAT promotes exhaustion of activated CD8⁺ T cells.

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Direct regulation of T cell exhaustion by NFAT

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-02-13 | E-GEOD-64409 | biostudies-arrayexpress

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