A recombinant extracellular domain of the human interleukin 4 receptor inhibits the biological effects of interleukin 4 on T and B lymphocytes.
Human interleukin 4 (IL4) acts on various hematopoietic cell types through interaction with a specific cell surface receptor (IL4R), whose cDNA has been cloned. We have produced a cDNA encoding a soluble form of the extracellular domain of the human IL 4R (sIL4R) and describe here the capacity of sIL4R to antagonize the in vitro activities of IL4 on normal B and T lymphocytes. sIL4R inhibited IL4-induced proliferation of both phytohemagglutinin-preactivated peripheral blood mononuclear cells (PBMC) and anti-IgM co-stimulated tonsil B cells with similar efficiency. This inhibitory activity was specific since sIL4R did not affect IL2-dependent proliferation of these cells. sIL4R also blocked IL4-dependent induction of the low-affinity receptor for IgE on B cells and inhibited IgE production by IL4-activated PBMC. Thus, in contrast to the IL6R extracellular domain which stimulates IL6 biological activity, the IL4R extracellular domain is a powerful antagonist of its specific ligand.
Garrone
P
P
Schering-Plough, Laboratory for Immunological Reseach, Dardilly, France.
Djossou
O
O
Galizzi
J P
JP
Banchereau
J
J
D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D001402:B-Lymphocytes / Q000187:drug effects*; D002478:Cells, Cultured; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000037:antagonists & inhibitors*; D008213:Lymphocyte Activation / Q000187:drug effects; D011961:Receptors, Fc / Q000032:analysis; D017455:Receptors, IgE; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects*
D000888:Antibodies, Anti-Idiotypic; D000944:Antigens, Differentiation, B-Lymphocyte; D007075:Immunoglobulin M; D007376:Interleukin-2; D011961:Receptors, Fc; D017455:Receptors, IgE; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D011994:Recombinant Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E