Journal
IMMUNOLOGY AND CELL BIOLOGY
Volume 86, Issue 7, Pages 622-630Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/icb.2008.43
Keywords
Herpesvirus saimiri; IFN-gamma; NF-kappa B; T-cell transformation; Th1 differentiation
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Funding
- German-Israeli Foundation (GIF) [674]
- German Research Foundation (DFG) [SFB466, GRK1071/C3, Bi465/5-1]
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Interferon-gamma (IFN-gamma) is an essential regulator of innate and adaptive immune responses and a hallmark of the Th1 T-cell subset. It is produced at high levels by human T lymphocytes upon transformation with Herpesvirus saimiri, which depends on the expression of the viral oncoproteins saimiri transformation-associated protein of subgroup C (StpC) and tyrosine kinase-interacting protein (Tip). Here, we show that IFN-gamma production was induced by Tip in Jurkat T cells. StpC by itself did not affect IFN-gamma expression, but enhanced the effect of Tip. Our results substantiated the findings that StpC induces NF-kappa B activation and demonstrated that other transcription factors, including NFAT, AP-1 and serum response element regulators, were not activated by StpC in unstimulated T cells. Studies using StpC mutants deficient in NF-kappa B activation, dominant negative I kappa B alpha and constitutively active IKK2, established the importance of NF-kappa B in StpC-mediated upregulation of IFN-gamma production. These observations suggest that NF-kappa B induction by StpC contributes to the Th1-like phenotype of virus-transformed human T cells.
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