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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.

Pubmed ID: 8384701

Authors

  • Kopf M
  • Le Gros G
  • Bachmann M
  • Lamers MC
  • Bluethmann H
  • K√∂hler G

Journal

Nature

Publication Data

March 18, 1993

Associated Grants

None

Mesh Terms

  • Alleles
  • Animals
  • Antibody Formation
  • Base Sequence
  • Cells, Cultured
  • Crosses, Genetic
  • Cytokines
  • DNA
  • Eosinophilia
  • Female
  • Gene Rearrangement
  • Heterozygote
  • Homozygote
  • Immunoglobulin A
  • Immunoglobulin E
  • Immunoglobulin G
  • Interferon-gamma
  • Interleukin-4
  • Interleukins
  • Kanamycin Kinase
  • Lymph Nodes
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred Strains
  • Molecular Sequence Data
  • Mutation
  • Nippostrongylus
  • Oligodeoxyribonucleotides
  • Phosphotransferases
  • Restriction Mapping
  • Strongylida Infections
  • T-Lymphocyte Subsets
  • T-Lymphocytes, Helper-Inducer
  • Transcription, Genetic