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

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
  • 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

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: