IL-10- and TGFβ-mediated Th9 Responses in a Human Helminth Infection

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. methodology: 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. principal findings: 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. conclusion: 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.