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Diminished immunopathology in Schistosoma mansoni infection following intranasal administration of cholera toxin B-immunodominant peptide conjugate correlates with enhanced transforming growth factor-beta production by CD4 T cells.

Abstract
In Schistosoma mansoni infection, CD4 T cells specific for parasite egg antigens mediate perioval granuloma formation in the liver and intestines. Mice of the CBA strain develop a severe form of disease and a significant proportion of their CD4 T cell response is directed against the major egg antigen Sm-p40 and its immunodominant T cell epitope peptide 234-246. Here, we show that intranasal (i.n.) treatment of infected CBA mice with a fusion protein of the cholera toxin B subunit (CTB) with peptide 234-246 (CTB::pep) results in significant down-modulation of hepatic granulomatous inflammation and fibrosis. Moreover, egg antigen-stimulated dispersed hepatic granuloma cells, as well as mesenteric lymph node CD4 T cells from the CTB::pep-treated mice, produced significantly more transforming growth factor (TGF)-beta than that produced by treated or untreated controls. The data demonstrate that i.n. administration of a single immunodominant peptide conjugated to CTB can lead to down-regulation of the hepatic immunopathology associated with schistosomiasis, and that this down-regulation is, at least in part, mediated by TGF-beta.
AuthorsHector J Hernandez, Laura I Rutitzky, Mike Lebens, Jan Holmgren, Miguel J Stadecker
JournalParasite immunology (Parasite Immunol) Vol. 24 Issue 8 Pg. 423-7 (Aug 2002) ISSN: 0141-9838 [Print] England
PMID12406196 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antigens, Helminth
  • Helminth Proteins
  • Immunodominant Epitopes
  • Peptide Fragments
  • Transforming Growth Factor beta
  • cholera toxin B-immunodominant peptide conjugate (234-246)
  • p40 egg antigen, Schistosoma
  • Cholera Toxin
Topics
  • Administration, Intranasal
  • Animals
  • Antigens, Helminth (administration & dosage, immunology)
  • CD4-Positive T-Lymphocytes (immunology, metabolism)
  • Cholera Toxin (administration & dosage, immunology)
  • Granuloma (immunology)
  • Helminth Proteins
  • Immunodominant Epitopes (chemistry, immunology)
  • Mice
  • Mice, Inbred CBA
  • Peptide Fragments (administration & dosage, immunology)
  • Schistosoma mansoni (immunology, pathogenicity)
  • Schistosomiasis mansoni (immunology, microbiology, pathology)
  • Snails
  • Transforming Growth Factor beta (biosynthesis)

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