Inability of interleukin-12 to modulate T-helper 0 effectors to T-helper 1 effectors: a possible distinct subset of T cells.
Interleukin-12 (IL-12) strongly favours the development of T-helper 1 (Th1)-type cells through its ability to induce interferon-gamma (IFN-gamma) production by natural killer cells and T cells. In the present work we analysed the effects of IL-12 on the synthesis and secretion of IFN-gamma and IL-4 by human T-cell clones. Several previously described human T-cell clones exhibiting Th1, Th2 or Th0 phenotypes were used for these analyses. We demonstrated, by enzyme-linked immunosorbent assay (ELISA) and intracytoplasmic staining, that, in Th0 clones, IL-12 up-regulated the production of both IFN-gamma and IL-4 and was unable to modulate these cells to Th1-type. The up-regulation of cytokine gene expression was transcriptionally regulated and was not due to differences in mRNA stability. In Th1 cells, IL-12 up-regulated only IFN-gamma and not IL-4. However, in Th2 cells, both IFN-gamma and IL-4 were up-regulated by IL-12. This suggests that Th2 cells may be less stable than Th1 cells. We also observed that human Th2 cells expressed the IL-12beta2 receptor, in contrast to murine Th2, which lacks this receptor. The observed differences in the effects of IL-12 on the three T-cell subsets may have important ramifications for IL-12-based therapies.
Hu
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Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Salgame
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P
D015152:Blotting, Northern; D018929:Cell Culture Techniques; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D018664:Interleukin-12 / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000276:immunology
D012333:RNA, Messenger; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma