Regulation of gene expression in lectin-stimulated or lymphokine-stimulated T lymphocytes: Effects of cyclosporine

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 ≈ 9 0%, CsA suppressed, to different extents, the phytohemagglutinin-stimulated expression of various genes, with levels of mRNAs for IL-2 being inhibited by ≈ 1 0 0%, c-myc and N-ras by ≈ 8 0%, and cfos 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 particulargene, and suggest that CsA interferes with only some of these regulatory pathways of gene expression in T lymphocytes.