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. 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., beta-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 beta-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.
Herblot
S
S
Laboratoire d'Immunologie Moléculaire, Université de Bordeaux II, France.
Chastagner
P
P
Samady
L
L
Moreau
J L
JL
Demaison
C
C
Froussard
P
P
Liu
X
X
Bonnet
J
J
Thèze
J
J
D000818:Animals; D001483:Base Sequence / Q000276:immunology; D002460:Cell Line; D003599:Cytoskeleton / Q000502:physiology*; D005786:Gene Expression Regulation / Q000276:immunology*; D006579:Heterozygote; D006720:Homozygote; D007376:Interleukin-2 / Q000235:genetics / Q000502:physiology*; D008198:Lymph Nodes / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D009857:Oncogenes / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology*
D007376:Interleukin-2; D012333:RNA, Messenger