IL-2-dependent expression of genes involved in cytoskeleton organization, oncogene regulation, and transcriptional control

IL-2 induces growth, differentiation, and/or apoptosis of lymphoid cells. T o study further the molecular basis of IL-2 function; we used a cDNA subtra ction approach involving a cell line grown in IL-2 or IL-4. From the corres ponding library, 66 nonredundant sequences were characterized; 16 of them e ncode identified proteins. The kinetics of in vitro expression of 8 selecte d sequences, the functions of which could he associated with IL-2-induced T cell activation/differentiation, was investigated using an IL-2-dependent T cell lint. IL-2 increased the expression of cytoskeleton proteins (cy-tub ulin), oncogene-regulating proteins (CCCTC-binding factor, Jun inhibitor fa ctor-1), and transcription factors (E2F-4, cyclic AMP-responsive element-bi nding protein, zhx-1), IL-2 also regulated the expression of genes coding f or multifunctional proteins, e.g., beta-catenin and nucleolin, These result s were verified using Con A-induced T cell blasts stimulated or not by IL-2 . The in vivo expression of four of these genes was also analyzed in spleen and lymph node cells of IL-2-deficient and MRL/lpr mice, which both have h igh numbers of activated cells, but the latter have intact IL-2 expression. The expression of beta-catenin, CCCTC-binding factor, Jun inhibitor factor -1, and nucleolin was significantly higher in MRL/lpr animals. A similar an alysis of thymocytes from IL-2(-/-) and IL-2(+/-) mice demonstrated the sam e expression patterns of the 4 sequences in these strains. The expression o f the IL-2-induced genes described herein is similar to the regulatory patt ern of IL-2R alpha. Taken together, our data provide additional evidence fo r the pleiotropic action of IL-2 in the periphery and IL-2 independence of molecular processes involved in thymocyte differentiation.