Distinct mechanisms of c-myc and lymphokine gene expression in an antigen specific T cell clone

Experiments were performed to examine the mechanisms regulating the expression of the c-myc gene and the IL-2 and interferon gamma (IFN-gamma) lymphokine genes in an antigen-specific murine T cell clone. IL-2 and the mitogenic lectin, concanavalin A (Con A), as well as the calcium ionophore ionomycin, in concert with phorbol ester, (PMA) enhanced c-myc gene transcription, but by distinct mechanisms as demonstrated by differential sensitivity to inhibition of protein synthesis and by transcriptional run-off assays using c-myc exon 1 and exon 2 probes. Induction of c-myc expression by IL-2, but not lectin or ionomycin plus phorbol ester, was inhibited in the presence of cycloheximide. IL-2 induced the transcription of both c-myc exons 1 and 2, whereas Con A primarily enhanced exon 1 to exon 2 transcriptional read-through. A direct relationship was observed between the level of early c-myc expression following IL-2 stimulation and the magnitude of the subsequent clonal proliferative response. Lymphokine gene expression was enhanced by Con A, but not by IL-2. Induction of the lymphokine genes in this T cell clone was under predominant post-transcriptional control and was sensitive to protein synthesis inhibition. Therefore, mitogenic lectins induce c-myc and lymphokine gene expression via different pathways.