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Laboratoire dImmunologie Moléculaire, Université de Bordeaux II, Bordeaux, France;
Unité dImmunogénétique Cellulaire, Institut Pasteur, Paris, France; and
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
(
-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
. 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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