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The Journal of Immunology, 1999, 162: 3280-3288.
Copyright © 1999 by The American Association of Immunologists

IL-2-Dependent Expression of Genes Involved in Cytoskeleton Organization, Oncogene Regulation, and Transcriptional Control1

Sabine Herblot2,*,{dagger}, Patricia Chastagner{dagger}, Laila Samady{dagger}, Jean-Louis Moreau{dagger}, Christophe Demaison3,{dagger}, Patrick Froussard{dagger}, Xinyuan Liu{ddagger}, Jacques Bonnet* and Jacques Thèze4,{dagger}

* Laboratoire d’Immunologie Moléculaire, Université de Bordeaux II, Bordeaux, France; {dagger} Unité d’Immunogénétique Cellulaire, Institut Pasteur, Paris, France; and {ddagger} Shanghai Institute of Biochemistry, Shanghai, China

IL-2 induces growth, differentiation, and/or apoptosis of lymphoid cells. To study further the molecular basis of IL-2 function, we used a cDNA subtraction approach involving a cell line grown in IL-2 or IL-4. From the corresponding library, 66 nonredundant sequences were characterized; 16 of them encode identified proteins. The kinetics of in vitro expression of 8 selected sequences, the functions of which could be associated with IL-2-induced T cell activation/differentiation, was investigated using an IL-2-dependent T cell line. IL-2 increased the expression of cytoskeleton proteins ({alpha}-tubulin), oncogene-regulating proteins (CCCTC-binding factor, Jun inhibitor factor-1), and transcription factors (E2F-4, cyclic AMP-responsive element-binding protein, zhx-1). IL-2 also regulated the expression of genes coding for multifunctional proteins, e.g., ß-catenin and nucleolin. These results 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 high numbers of activated cells, but the latter have intact IL-2 expression. The expression of ß-catenin, CCCTC-binding factor, Jun inhibitor factor-1, and nucleolin was significantly higher in MRL/lpr animals. A similar analysis of thymocytes from IL-2-/- and IL-2+/- mice demonstrated the same expression patterns of the 4 sequences in these strains. The expression of the IL-2-induced genes described herein is similar to the regulatory pattern of IL-2R{alpha}. Taken together, our data provide additional evidence for the pleiotropic action of IL-2 in the periphery and IL-2 independence of molecular processes involved in thymocyte differentiation.




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