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Blood, Vol. 93 No. 6 (March 15), 1999:
pp. 1980-1991
Interferon- Activates Multiple STAT Proteins and Upregulates
Proliferation-Associated IL-2R, c-myc,
and pim-1 Genes in Human T Cells
Sampsa Matikainen,
Timo Sareneva,
Tapani Ronni,
Anne Lehtonen,
Päivi J. Koskinen, and
Ilkka Julkunen
From the Department of Virology, National Public Health Institute,
Helsinki, Finland; and Turku Centre for Biotechnology,
University of Turku and Åbo Akademi University, Turku, Finland.
Interferon- (IFN-) is a pleiotropic cytokine that has
antiviral, antiproliferative, and immunoregulatory functions. There is
increasing evidence that IFN- has an important role in T-cell biology. We have analyzed the expression of
IL-2R, c-myc, and pim-1 genes
in anti-CD3-activated human T lymphocytes. The induction of these
genes is associated with interleukin-2 (IL-2)-induced T-cell
proliferation. Treatment of T lymphocytes with IFN-, IL-2, IL-12,
and IL-15 upregulated IL-2R, c-myc, and
pim-1 gene expression. IFN- also sensitized T cells to
IL-2-induced proliferation, further suggesting that IFN- may be
involved in the regulation of T-cell mitogenesis. When we analyzed the
nature of STAT proteins capable of binding to IL-2R,
pim-1, and IRF-1 GAS elements after cytokine stimulation, we observed IFN--induced binding of STAT1, STAT3, and
STAT4, but not STAT5 to all of these elements. Yet, IFN- was able to
activate binding of STAT5 to the high-affinity IFP53 GAS site.
IFN- enhanced tyrosine phosphorylation of STAT1, STAT3, STAT4,
STAT5a, and STAT5b. IL-12 induced STAT4 and IL-2 and IL-15 induced
STAT5 binding to the GAS elements. Taken together, our results suggest
that IFN-, IL-2, IL-12, and IL-15 have overlapping activities on
human T cells. These findings thus emphasize the importance of IFN-
as a T-cell regulatory cytokine.
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