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CD4 T cells producing pro-inflammatory interleukin-17 mediate high pathology in schistosomiasis.

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.
AuthorsLaura I Rutitzky, Miguel J Stadecker
JournalMemoĢrias do Instituto Oswaldo Cruz (Mem Inst Oswaldo Cruz) Vol. 101 Suppl 1 Pg. 327-30 (Sep 2006) ISSN: 0074-0276 [Print] Brazil
PMID17308791 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Antigens, Helminth
  • Interleukin-17
Topics
  • Animals
  • Antigens, Helminth (administration & dosage)
  • CD4-Positive T-Lymphocytes (immunology)
  • Inflammation (immunology, prevention & control)
  • Interleukin-17 (analysis, immunology)
  • Mice
  • Mice, Inbred C57BL
  • Schistosoma mansoni (immunology)
  • Schistosomiasis (immunology, pathology)
  • Severity of Illness Index

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