IL-4 inhibits the synthesis of IFN-γ and induces the synthesis of IgE in human mixed lymphocyte cultures

D. Vercelli, H. H. Jabara, R. P. Lauener, R. S. Geha

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Abstract

The T cell-derived lymphokine IL-4 is essential for the induction of IgE synthesis by human lymphocytes. The IgE-inducing effect of IL-4 is antagonized by IFN-γ. The secretion of IFN-γ is vigorously triggered in MLC. Thus, IL-4-stimulated MLC represent a suitable model to characterize the functional antagonism between IL-4 and IFN-γ. In this report, we show that rIL-4 consistently induced IgE synthesis when added to human primary MLC. IL-4-dependent IGE production required cognate T/B cell recognition, because it was inhibited by antibodies to CD3 and MHC class II (HLA-DR) Ag. A neutralizing anti-IFN-γ mAb dramatically enhanced IL-4-dependent IgE synthesis by MLC, indicating that endogenous IFN-γ is a major inhibitor of IgE production. More importantly, addition of rIL-4 markedly inhibited the release of IFN-γ in supernatants of MLC and Con A-activated PBMC. The decrease in IFN-γ protein was accompanied by a decreased expression of IFN-γ mRNA transcripts. The downregulation of IFN-γ by IL-4 is likely to play an important role in the IL-4-dependent induction of IgE synthesis.

Original languageEnglish (US)
Pages (from-to)570-573
Number of pages4
JournalJournal of Immunology
Volume144
Issue number2
StatePublished - Jan 1 1990
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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