IL-12 TRANSIENTLY INDUCES IFN-GAMMA TRANSCRIPTION AND PROTEIN-SYNTHESIS IN HUMAN CD4+ ALLERGEN-SPECIFIC T(H)2 T-CELL CLONES

IL-12 is a cytokine produced by monocytes and Epstein-Barr virus-transformed B cells which initiates T(h)1 responses by inducing the development of CD4+, IFN-gamma producing T(h)1 T cells in mouse and human. We have previously reported that allergen-specific CD4+ T(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-1 2 on the cytokine production profiles of a panel of cloned allergen-specific T(h)2 cell lines, and compare these to the effects of rIL-12 on the cytokine production by T(h)0 and Th(1) T cell clones. Activation with antigen or TPA/anti-CD3 mAb of T(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(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(h)0 and T(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(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(h)0 type of cytokine production profile in T(h)2 T cells.