International Immunology, Vol. 13, No. 2, 135-147,
February 2001
© 2001 Japanese Society for Immunology
IL-2-induced tumor necrosis factor (TNF)-ß expression: further analysis in the IL-2 knockout model, and comparison with TNF-
, lymphotoxin-ß, TNFR1 and TNFR2 modulation
Unité d'Immunogénétique Cellulaire and
1 Unité d'Histopathologie, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France
2 Shanghai Institute of Biochemistry, 320 Yue Yang Road, Shanghai 200031, China
Correspondence to: Correspondence to: J. Thèze
IL-2 induces the stimulation of inflammatory and immune reactions, and the apoptosis of antigen-activated cells. However, the molecular basis of these pleiotropic functions is largely unknown. We have previously reported that IL-2 induces genes involved in cytoskeleton organization, oncogene regulation and transcriptional control. In an IL-2-dependent cell line, we have also shown that IL-2 induces tumor necrosis factor (TNF)-ß mRNA through the Jak–STAT pathway. Here, we first demonstrate in vitro that IL-2 induces mature and partially spliced TNF-ß mRNA in the splenocytes and lymph node cells of both IL-2–/– and IL-2+/– mice. Under the same experimental conditions, IL-2 is seen to induce TNF-
mRNA. mRNA expression is followed by semiquantitative RT-PCR and this analysis is then extended in vivo by studying different lymphoid organs from IL-2–/–animals. Strikingly, the expression of TNF-ß mRNA is noted to be extremely low in the spleens and lymph nodes of IL-2–/– mice. Similarly, TNF-, lymphotoxin (LT)-ß, TNFR1 and TNFR2 mRNA levels are also low in the spleens of IL-2–/– animals, whereas IFN-
and IL-4 mRNA levels remain unaffected in these animals. The experimental values are significantly different (P 
0.05) from those of control IL-2+/– animals. Western blot analysis of TNF- expression confirmed and extended the results at the protein level. For the first time, we demonstrate that IL-2 directly or indirectly regulates genes of the TNF–TNFR family in secondary lymphoid organs. Furthermore, IL-2–/– animals in which thymopoiesis is unaffected show normal expression of these genes. Altogether, our data further define the pleiotropic effects of IL-2 at the molecular level.
Keywords: cytokines, cytokine receptors, knockout
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