학술논문

Impaired NFAT nuclear translocation results in split exhaustion of virus-specific CD8+ T cell functions during chronic viral infection.
Document Type
Article
Source
Proceedings of the National Academy of Sciences of the United States of America. 3/13/2007, Vol. 104 Issue 11, p4565-4570. 6p. 5 Graphs.
Subject
*T cells
*VIRUS diseases
*IMMUNE system
*ANTIGENS
*IMMUNOPATHOLOGY
*LYMPHOCYTIC choriomeningitis
Language
ISSN
0027-8424
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 Ca2+ 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. [ABSTRACT FROM AUTHOR]