title: IL-10- and TGFβ-mediated Th9 Responses in a Human Helminth Infection.
abstract: BACKGROUND
  Th9 cells are a subset of CD4+ T cells that express the protoypical cytokine, IL-9. Th9 cells are known to effect protective immunity in animal models of intestinal helminth infections. However, the role of Th9 cells in human intestinal helminth infections has never been examined.
  
  
  METHODS
  To examine the role of Th9 cells in Strongyloidis stercoralis (Ss), a common intestinal helminth infection, we compared the frequency of Th9 expressing IL-9 either singly (mono-functional) or co-expressing IL-4 or IL-10 (dual-functional) in Ss-infected individuals (INF) to frequencies in uninfected (UN) individuals.
  
  
  RESULTS
  INF individuals exhibited a significant increase in the spontaneously expressed and/or antigen specific frequencies of both mono- and dual-functional Th9 cells as well as Th2 cells expressing IL-9 compared to UN. The differences in Th9 induction between INF and UN individuals was predominantly antigen-specific as the differences were no longer seen following control antigen or mitogen stimulation. In addition, the increased frequency of Th9 cells in response to parasite antigens was dependent on IL-10 and TGFx since neutralization of either of these cytokines resulted in diminished Th9 frequencies. Finally, following successful treatment of Ss infection, the frequencies of antigen-specific Th9 cells diminished in INF individuals, suggesting a role for the Th9 response in active Ss infection. Moreover, IL-9 levels in whole blood culture supernatants following Ss antigen stimulation were higher in INF compared to UN individuals.
  
  
  CONCLUSIONS
  Thus, Ss infection is characterized by an IL-10- and TGFβ dependent expansion of Th9 cells, an expansion found to reversible by anti-helmintic treatment.
authors.affiliation: National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India.
authors.forename: Rajamanickam
authors.initials: R
authors.lastname: Anuradha
authors.affiliation: National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India.
authors.forename: Saravanan
authors.initials: S
authors.lastname: Munisankar
authors.affiliation: National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India.
authors.forename: Yukthi
authors.initials: Y
authors.lastname: Bhootra
authors.affiliation: National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India.
authors.forename: Jeeva
authors.initials: J
authors.lastname: Jagannathan
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: Chandrakumar
authors.initials: C
authors.lastname: Dolla
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: Paul
authors.initials: P
authors.lastname: Kumaran
authors.affiliation: Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
authors.affiliation: National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India.|Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Subash
authors.initials: S
authors.lastname: Babu
mesh_terms: D000293:Adolescent; D000328:Adult; D015766:Albendazole / Q000627:therapeutic use; D000977:Antiparasitic Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D007559:Ivermectin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D013322:Strongyloidiasis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000977:Antiparasitic Agents; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007559:Ivermectin; D015766:Albendazole