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

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‐myc and N‐ras by ≈80%, and c‐fos and 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 the c‐myc and 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.