title: 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.
authors.affiliation: Institute of Microbiology, Eidgenössische Technische Hochschule, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
authors.forename: Paola
authors.initials: P
authors.lastname: Agnellini
authors.forename: Petra
authors.initials: P
authors.lastname: Wolint
authors.forename: Manuela
authors.initials: M
authors.lastname: Rehr
authors.forename: Julia
authors.initials: J
authors.lastname: Cahenzli
authors.forename: Urs
authors.initials: U
authors.lastname: Karrer
authors.forename: Annette
authors.initials: A
authors.lastname: Oxenius
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002118:Calcium / Q000378:metabolism; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis; D005434:Flow Cytometry; D006678:HIV / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism; D007107:Immune System; D051379:Mice; D008810:Mice, Inbred C57BL; D050778:NFATC Transcription Factors / Q000378:metabolism* / Q000502:physiology*; D010477:Perfusion; D019076:Transgenes
chemical_list: D016207:Cytokines; D050778:NFATC Transcription Factors; D002118:Calcium