IL-12 transiently induces IFN- gamma transcription and protein synthesis in human CD4 super(+) allergen-specific T sub(h)2 T cell clones

IL-12 is a cytokine produced by monocytes and Epstein-Barr virus-transformed B cells which initiates T sub(h)1 responses by inducing the development of CD4 super(+), IFN- gamma producing T sub(h)1 T cells in mouse and human. We have previously reported that allergen-specific CD4 super(+) T sub(h)2 T cell clones produce IFN- gamma , following activation by phorbol ester (TPA) and calcium ionophore, indicating that these cells still have the ability to produce IFN- gamma . This observation, together with the capacity of IL-12 to induce IFN- gamma , prompted us to examine the effects of rIL-12 on the cytokine production profiles of a panel of cloned allergen-specific T sub(h)2 cell lines, and compare these to the effects of rIL-12 on the cytokine production by T sub(h)0 and T sub(h)1 T cell clones. Activation with antigen or TPA/anti-CD3 mAb of T sub(h)2 T cell clones that had been preincubated with rIL-12 and rIL-2 for 5 days induced or enhanced the expression of IFN- gamma transcripts, as well as the production of IFN- gamma by these cells. Furthermore, in a different set of experiments, it was found that the presence of rIL-12 during a 12 h stimulation of T sub(h)2 T cell clones induced or enhanced the expression of IFN- gamma transcripts, as well as the production of IFN- gamma by these cells. rIL-12 also enhanced IFN- gamma production by T sub(h)0 and T sub(h)1 T cells, but, in contrast, rIL-12 had no effect on the production of IL-4, nor on the frequency of IL-4 producing cells, as judged by analysis of intracellularly produced cytokines. Continuous culture of these T sub(h)2 T cell clones in the absence of rIL-12 resulted in a decreased or non-detectable production of IFN- gamma by the cells following antigen-specific activation, indicating that the inducing and enhancing effects of rIL-12 on the IFN- gamma production is transient. Together these results show that rIL-12, through its specific IFN- gamma -inducing capacities, can induce a T sub(h)0 type of cytokine production profile in T sub(h)2 T cells.