REGULATION OF GENE EXPRESSION IN LECTIN-STIMULATED OR LYMPHOKINE-STIMULATED T LYMPHOCYTES1

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Abstract
The effects of cyclosporine were examined on gene expression induced in T lymphocytes by mitogenic lectins and interleukin 2 (IL-2). Used at concentrations that inhibited proliferation of human peripheral blood lymphocytes by ≈90%, CsA suppressed, to different extents, the phytohemagglutinin-stimulated expression of various genes, with levels of mRNAs for IL-2 being inhibited by ≈100%,c-mycandN-rasby ≈80%, and c-fosand IL-2 receptors by ≈50%. Comparisons of the actions of CsA on gene expression in a cloned murine T cell (L2), stimulated with concanavalin A or IL-2, demonstrated that CsA specifically blocked the accumulation of mRNAs for thec-mycand p53 protooncogenes when induced by Con A, but not when induced by IL-2. Taken together, these findings indicate that several pathways can control the expression of a particular gene, and suggest that CsA interferes with only some of these regulatory pathways of gene expression in T lymphocytes.

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