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

M Kopf, GL Gros, M Bachmann, MC Lamers… - Nature, 1993 - nature.com
M Kopf, GL Gros, M Bachmann, MC Lamers, H Bluethmann, G Köhler
Nature, 1993nature.com
MURINE T-helper clones are classified into two distinct subsets (Thl and Th2) on the basis of
their patterns of lymphokine secretion. Thl clones secrete interleukin-2 (IL-2), tumour
necrosis factor-β (TNF-β) and interferon-γ (IFN-γ), 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-γ and
differentially promote antibody or delayed-type hypersensitivity responses2, 3. To evaluate
whether IL-4 is required for mounting Th2 responses, we generated IL-4-mutant mice (IL-4 …
Abstract
MURINE T-helper clones are classified into two distinct subsets (Thl and Th2) on the basis of their patterns of lymphokine secretion. Thl clones secrete interleukin-2 (IL-2), tumour necrosis factor-β (TNF-β) and interferon-γ (IFN-γ), 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-γ and differentially promote antibody or delayed-type hypersensitivity responses2,3. To evaluate whether IL-4 is required for mounting Th2 responses, we generated IL-4-mutant mice (IL-4–/ –)4,5 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 vivo6. 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.
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