IL-4 inhibits the synthesis of IFN-gamma and induces the synthesis of IgE in human mixed lymphocyte cultures.
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-gamma. The secretion of IFN-gamma is vigorously triggered in MLC. Thus, IL-4-stimulated MLC represent a suitable model to characterize the functional antagonism between IL-4 and IFN-gamma. 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-gamma mAb dramatically enhanced IL-4-dependent IgE synthesis by MLC, indicating that endogenous IFN-gamma is a major inhibitor of IgE production. More importantly, addition of rIL-4 markedly inhibited the release of IFN-gamma in supernatants of MLC and Con A-activated PBMC. The decrease in IFN-gamma protein was accompanied by a decreased expression of IFN-gamma mRNA transcripts. The downregulation of IFN-gamma by IL-4 is likely to play an important role in the IL-4-dependent induction of IgE synthesis.
Vercelli
D
D
Division of Immunology, Children's Hospital, Boston, MA.
Jabara
H H
HH
Lauener
R P
RP
Geha
R S
RS
D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology*; D015152:Blotting, Northern; D017252:CD3 Complex; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D015847:Interleukin-4 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D012333:RNA, Messenger / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D006684:HLA-DR Antigens; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma