IL-12 transiently induces IFN-gamma transcription and protein synthesis in human CD4+ allergen-specific Th2 T cell clones.
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)
Yssel
H
H
DNAX Research Institute for Molecular and Cellular Biology, Human Immunology Department, Palo Alto, CA 94304-1104.
Fasler
S
S
de Vries
J E
JE
de Waal Malefyt
R
R
D000485:Allergens / Q000276:immunology*; D002999:Clone Cells; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D018664:Interleukin-12 / Q000276:immunology*; D008213:Lymphocyte Activation; D011994:Recombinant Proteins / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D014158:Transcription, Genetic
D000485:Allergens; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma