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.
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.
Hernandez
Hector J
HJ
Department of Pathology, Tufts University School of Medicine, Boston, MA 02111, USA. miguel.stadecker@tufts.edu
Rutitzky
Laura I
LI
Lebens
Mike
M
Holmgren
Jan
J
Stadecker
Miguel J
MJ
D000281:Administration, Intranasal; D000818:Animals; D000947:Antigens, Helminth / Q000008:administration & dosage / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology*; D006099:Granuloma / Q000276:immunology; D015801:Helminth Proteins; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*; D012550:Schistosoma mansoni / Q000276:immunology* / Q000472:pathogenicity; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D012908:Snails; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D000947:Antigens, Helminth; D015801:Helminth Proteins; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D016212:Transforming Growth Factor beta; C470603:cholera toxin B-immunodominant peptide conjugate (234-246); C055560:p40 egg antigen, Schistosoma; D002772:Cholera Toxin