Regulation of human IgE synthesis: The role of CD4+ and CD8+ T-cells and the inhibitory effects of interferon-α

J. F. Gauchat, H. Gascan, M. G. Roncarolo, F. Rousset, J. Pene, J. E. De Vries

Research output: Contribution to journalArticle

Abstract

Interleukin-4 (IL-4) has been shown to induce immunoglobulin E (IgE) synthesis by human peripheral blood lymphocytes (PBL). Here we show that highly purified B-cells (> 99.5%) failed to produce IgE In the presence of IL-4 but IgE synthesis was restored by the addition of autologous CD4+ T-cells or by CD4+ T-cell clones with non-relevant specificities, derived from different donors. In contrast, autologous CD8+ T-lymphocytes or one allogeneic CD8+ T-cell clone failed to restore IgE synthesis. Moreover, autologous CD8+ T-cells suppressed IgE synthesis induced by autologous CD4+ T-cells in a dose-dependent fashion. IgE production could be induced in cultures containing as few as 20 B-cells. Collectively these data indicate that in addition to IL-4, a second signal derived from CD4+ T-cells is required to induce B-cells to switch to IgE producing cells. In a second set of experiments we showed that IFN-α blocked both IL-4-induced IgE synthesis by PBL of healthy donors and spontaneous IgE synthesis by PBL of allergic or atopic patients in a dose-dependent fashion. This inhibition occurred at the IgE messenger ribonucleic acid (mRNA) transcription level. The strongest inhibitory effects of interferon-α (IFN-α) were observed at the 2.2 kb productive mRNA transcript, whereas weaker inhibitory effects were observed on the 1.7 kb germline IgE mRNA transcript. Finally, it was shown that administration of 3 x 106 of IFN-α subcutaneously (sc) twice a week for a period of four weeeks to a patient with the hyper IgE syndrome with eczema resulted in a reduction in serum IgE levels of 50% and a transient disappearance of the eczema. These results indicate that IFN-α is also effective in inhibiting IgE synthesis in vivo.

Original languageEnglish
JournalEuropean Respiratory Journal, Supplement
Volume4
Issue number13
Publication statusPublished - 1991

Keywords

  • Allergy
  • Immunoglobulin E synthesis
  • Interferon-α
  • T-cells

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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    Gauchat, J. F., Gascan, H., Roncarolo, M. G., Rousset, F., Pene, J., & De Vries, J. E. (1991). Regulation of human IgE synthesis: The role of CD4+ and CD8+ T-cells and the inhibitory effects of interferon-α. European Respiratory Journal, Supplement, 4(13).