IL-12-induced activation of NK and T cells occurs in the absence of immediate-early activation gene expression.
The responses of lymphocytes to IL-2 and IL-12, involving proliferation, differentiation, and cytokine production, are only partially overlapping, and may depend on induced differential expression of specific sets of genes. Using reverse-transcription PCR differential display, we isolated an mRNA species expressed in IL-2- but not IL-12-stimulated NK cells. This was identified as the mRNA encoding the transcription factor egr-1, which is expressed with fast kinetics in T and NK cells upon IL-2, but not IL-12, stimulation. Analysis of the accumulation of mRNA-encoding members of the AP-1 transcription factor family demonstrated that c-fos and junB are also expressed upon stimulation of NK and T cells with IL-2, but not IL-12, whereas expression of c-jun and junD is not modified by either cytokine. Accordingly, increased AP-1 DNA-binding activity and AP-1-dependent transcriptional activity were detected exclusively in IL-2-stimulated cells. Analysis of the expression of genes reported to regulate cytokine-induced proliferation demonstrated that both IL-2 and IL-12 induce c-myc mRNA accumulation in NK and T cells, whereas only IL-2 induces bcl-2 expression. Our data provide the first demonstration that IL-12-mediated activation of T and NK cells does not involve expression of members of the immediate-early activation genes family (egr-1, c-fos, and junB), AP-1 transcriptional activity, or bcl-2 expression. This indicates that functional differences observed in IL-2- and IL-12-stimulated cells may depend, at least in part, on differential gene regulation.
Azzoni
L
L
Kimmel Cancer Institute, Jefferson Medical College, Philadelphia, PA 19107, USA.
Kanakaraj
P
P
Zatsepina
O
O
Perussia
B
B
D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051766:Early Growth Response Protein 1; D005786:Gene Expression Regulation; D017781:Genes, Immediate-Early; D016762:Genes, fos; D016758:Genes, jun; D016259:Genes, myc; D006801:Humans; D017874:Immediate-Early Proteins; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D018808:Transcription Factor AP-1 / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D007376:Interleukin-2; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D018664:Interleukin-12