IL-12 transiently induces IFN-_γ transcription and protein synthesis in human CD4 ⁺ allergen-specific T_h2 T cell clones

Abstract

IL-12 is a cytokine produced by monocytes and Epstein-Barr virus-transformed B cells which initiates Th1 responses by inducing the development of CD4+, IFN-gamma producing Th1 T cells in mouse and human. We have previously reported that allergen-specific CD4+ Th2 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 Th2 cell lines, and compare these to the effects of rIL-12 on the cytokine production by Th0 and Th1 T cell clones. Activation with antigen or TPA/anti-CD3 mAb of Th2 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 Th2 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 Th0 and Th1 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.(ABSTRACT TRUNCATED AT 250 WORDS)

CpG Motifs as Possible Adjuvants for the Treatment of Allergic Diseases

“…IFN-α, on the other hand, acted directly on Th2 cells and drove Th1 development by activating STAT-4, a transcription factor necessary for IFN-γ induction [46]. Although several studies suggested that established Th2 populations remained susceptible to IL-12-dependent reversal to IFN-γ producing phenotypes [47, 48]additional support to accomplish this immunomodulation could result from the induction of CpG-ODN-induced IFN-α in APC.…”

Selective expression of an interleukin-12 receptor component by human T helper 1 cells

“…Time course experiments revealed that the IL-12 induced upregulation of the IL-12R ␤2 mRNA in primed T cells was transient; maximal induction was seen 24-48 h after the addition of IL-12, but returned to the level of the control cultures after 96 h (data not shown). The IL-12-induced transient upregulation of the IL-12R ␤2 transcripts in Th2 clones may account for the transient period of IFN-␥ production in cells with an established Th2 phenotype (35,36).…”

IFN-γ Up-Regulates IL-18 Gene Expression Via IFN Consensus Sequence-Binding Protein and Activator Protein-1 Elements in Macrophages

“…IFN-␥ is secreted mostly from T cells or NK cells when they are activated by Ags or mitogens. Among cytokines, IL-12 has been shown to be the major stimulator of IFN-␥ production by T cells (6,7). In addition, IL-2, TNF-␣, and IL-1 are known to be costimulators for the induction of IFN-␥ by NK cells (8).…”