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Institute for Immunology, Ruprecht-Karls-University, Heidelberg, Germany
Expression of the IL-2 gene requires activation of T cells through
stimulation of the TCR and costimulation through accessory receptors.
We have found recently that okadaic acid-sensitive Ser/Thr phosphatases
are involved in a cyclosporin A-insensitive pathway that selectively
transmits costimulatory signals. In this study, we analyzed whether
activities of these phosphatases are necessary for the expression of
the IL-2 gene. In both activated peripheral blood T lymphocytes and
activated tumorigenic T cell lines, IL-2 gene expression was blocked at
the transcriptional level by okadaic acid. The transcription factors
active at the IL-2 promoter were differentially influenced: upon
down-modulation of okadaic acid-sensitive phosphatases, transactivation
by octamer, NF-
B, and NF of activated T cells proteins was
abrogated, while transactivation by AP-1 proteins was even
enhanced.
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