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 proliferatio n, differentiation, and cytokine production, are only partially overla pping, and may depend on induced differential expression of specific s ets 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 f actor egr-1, which is expressed with fast kinetics in T and NK cells u pon IL-2, but not IL-12, stimulation. Analysis of the accumulation of mRNA-encoding members of the AP-1 transcription factor family demonstr ated 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 jun D is not modified by either cytokine. Accordingly, increased AP-1 DNA- binding activity and AP-l-dependent transcriptional activity were dete cted exclusively in IL-2-stimulated cells. Analysis of the expression of genes reported to regulate cytokine-induced proliferation demonstra ted 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 cel ls does not involve expression of members of the immediate-early activ ation genes family (egr-1, c-fos, and junB), AP-1 transcriptional acti vity, or bcl-2 expression. This indicates that functional differences observed in IL-2- and IL-12-stimulated cells may depend, at least in p art, on differential gene regulation.