Disruption of the murine IL-4 gene blocks Th2 cytokine responses.
Murine T-helper clones are classified into two distinct subsets (Th1 and Th2) on the basis of their patterns of lymphokine secretion. Th1 clones secrete interleukin-2 (IL-2), tumour necrosis factor-beta (TNF-beta) and interferon-gamma (IFN-gamma), whereas Th2 clones secrete IL-4, IL-5 and IL-10 (ref. 1). These subsets are reciprocally regulated by IL-4, IL-10 and IFN-gamma and differentially promote antibody or delayed-type hypersensitivity responses. To evaluate whether IL-4 is required for mounting Th2 responses, we generated IL-4-mutant mice (IL-4-/-) and assessed the cytokine secretion pattern of T cells both from naive and Nippostrongylus brasiliensis infected mice. CD4+ T cells from naive IL-4-/- mice failed to produce Th2-derived cytokines after in vitro stimulation. The levels of Th2 cytokines IL-5, IL-9 and IL-10 from CD4+ T cells obtained after nematode infection were significantly reduced. The reduced IL-5 production in IL-4-/- mice correlated with reduced helminth-induced eosinophilia, which has been shown to be dependent on IL-5 in vivo. We conclude that IL-4 is required for the generation of the Th2-derived cytokines and that immune responses dependent on these cytokines are impaired.
Max-Planck-Institute for Immunology, Freiburg, Germany.
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M
Kopf
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Le Gros
M
M
Bachmann
M C
MC
Lamers
H
H
Bluethmann
G
G
Köhler
D000483:Alleles; D000818:Animals; D000917:Antibody Formation; D001483:Base Sequence; D002478:Cells, Cultured; D003433:Crosses, Genetic; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004802:Eosinophilia / Q000097:blood / Q000276:immunology; D005260:Female; D015321:Gene Rearrangement; D006579:Heterozygote; D006720:Homozygote; D007070:Immunoglobulin A / Q000097:blood; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000235:genetics*; D007378:Interleukins / Q000096:biosynthesis; D019868:Kanamycin Kinase; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009154:Mutation; D009559:Nippostrongylus; D009838:Oligodeoxyribonucleotides; D010770:Phosphotransferases / Q000235:genetics; D015183:Restriction Mapping; D017206:Strongylida Infections / Q000097:blood / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014158:Transcription, Genetic
D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007378:Interleukins; D009838:Oligodeoxyribonucleotides; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D004247:DNA; D010770:Phosphotransferases; D019868:Kanamycin Kinase