CD4 T cells producing pro-inflammatory interleukin-17 mediate high pathology in schistosomiasis.
Mem Inst Oswaldo Cruz
; 101 Suppl 1: 327-30, 2006 Sep.
Article
em En
| MEDLINE
| ID: mdl-17308791
ABSTRACT
In murine schistosomiasis mansoni, pronounced CD4 T cell-mediated, egg-induced, hepato-intestinal immunopathology and death, whether genetically determined or elicited experimentally, are associated with failure to down-regulate a net pro-inflammatory immune response. Important evidence contributing to this notion comes from the observation that immunization with schistosome egg antigens in CFA (SEA/CFA) causes low pathology C57BL/6 mice to develop an exacerbated form of disease and death in a cytokine milieu characterized by elevated interferon (IFN)-gamma levels. Since such a pro-inflammatory environment presumes a signaling pathway involving interleukin (IL)-12, the SEA/CFA immunization model was used to examine the extent of hepatic immunopathology in the absence of this cytokine. Surprisingly, the IL-12p40 subunit was an absolute requirement for the development of exacerbated disease, whereas the IL-12p35 subunit was not. Moreover, significantly elevated in vitro production of IL-17, but not of IFN-gamma, correlated with the high pathology, and neutralization of IL-17 in vivo resulted in a significant reduction of hepatic inflammation. Our findings clearly demonstrate the pathogenic potential of the novel IL-17-producing T cell subpopulation (ThIL-17), previously shown to mediate chronic inflammation in autoimmune disease. They also imply that IL-23, but not IL-12, is the critical signal necessary to support the pro-inflammatory ThIL-17 subset involved in high pathology schistosomiasis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Schistosoma mansoni
/
Esquistossomose
/
Linfócitos T CD4-Positivos
/
Interleucina-17
/
Inflamação
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mem Inst Oswaldo Cruz
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos