Disruption of the murine IL-4 gene blocks Th2 cytokine responses.

Journal article

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.

Authors: Kopf, M; Le Gros, G; Bachmann, M; Lamers, M; Bluethmann, H

• Publication status: Published
• Journal: Nature
• Volume: 362
• Issue: 6417
• Pages: 245-248
• Publication date: 1993-03-01
• DOI: 10.1038/362245a0
• EISSN: 1476-4687
• ISSN: 0028-0836
• Language: English
• Keywords: T-Lymphocytes, Helper-Inducer; Lymphocyte Activation; Mutation; Oligodeoxyribonucleotides; Interleukins; Interferon-gamma; Strongylida Infections; Cells, Cultured; Molecular Sequence Data; DNA; Mice, Inbred Strains; Transcription, Genetic; T-Lymphocyte Subsets; Male; Antibody Formation; Immunoglobulin A; Immunoglobulin G; Heterozygote; Immunoglobulin E; Gene Rearrangement; Mice; Interleukin-4; Restriction Mapping; Nippostrongylus; Base Sequence; Female; Crosses, Genetic; Eosinophilia; Animals; Lymph Nodes; Alleles; Phosphotransferases; Kanamycin Kinase; Homozygote; Cytokines