Interferon gamma is a key cytokine in lung phase immunity to schistosomes but what is its precise role?
Vaccination of mice with radiation-attenuated cercariae of Schistosoma mansoni induces a high level of protection against challenge with normal larvae. The immune effector mechanism, which operates in the lungs, is a cell-mediated delayed-type hypersensitivity response and involves the formation of a tight focus of mononuclear cells around embolised larvae. CD4+ T cells with Th1 characteristics are a major component of the infiltrate. They secrete abundant interferon gamma (IFN gamma) upon antigen stimulation in vitro, whilst in vivo neutralisation of the cytokine results in 90% abrogation of immunity. IFN gamma can induce a large number of genes and an attempt has been made to identify the ones which are essential components of the effector mechanism. Inducible nitric oxide synthase (iNOS) is such a candidate and nitric oxide (NO) is produced by cultures of airway leucocytes from the lungs of vaccinated mice post-challenge. However, the continued resistance of mice with a disrupted iNOS gene indicates that NO has only a minor role in the protective response. Mice with a disrupted IFN gamma receptor gene have been used to dissect the role of the cytokine. After vaccination and challenge, CD4+ T cells from the pulmonary interstitium have reduced levels of ICAM-1 and LFA-1 expression, compared to wild-type animals, which coincides with a reduced cohesiveness of foci. However, immunity is not significantly impaired in mice with a disrupted ICAM-1 gene, and focus formation is normal. Similarly, a role has not been found for CD2/CD48 interactions in cell aggregation. Possible IFN gamma-inducible molecules yet to be fully investigated include other ligand-receptor pairs, chemokines, and tumour necrosis factor alpha.
Wilson
R A
RA
Department of Biology, University of York, UK. raw3@york.ac.uk
D000818:Animals; D016207:Cytokines / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology*; D008168:Lung / Q000276:immunology*; D051379:Mice; D012550:Schistosoma mansoni / Q000472:pathogenicity*; D012555:Schistosomiasis mansoni / Q000276:immunology*
D016207:Cytokines; D007371:Interferon-gamma