CD25+CD4+ cells contribute to Th2 polarization during helminth infection by suppressing Th1 response development.
Mice infected with Schistosoma mansoni develop polarized Th2 responses in which Th1 responses are prevented by IL-10-mediated suppression of IL-12 production. We show that dendritic cells from infected mice are primed to make IL-12 in response to CD40 ligation, and that IL-10 acts by inhibiting this process. In infected mice, two subpopulations of CD4(+) cells, separable by their expression of CD25, make IL-10. CD25(+)CD4(+) cells expressed forkhead box P3, inhibited proliferation of CD4(+) T cells, and made IL-10, but little IL-5. In contrast, CD25(-)CD4(+) cells failed to express forkhead box P3 or to inhibit proliferation and accounted for all the IL-5, IL-6, and IL-13 produced by unseparated splenic populations. Thus, CD25(+) and CD25(-) subpopulations could be characterized as regulatory T cells (Treg cells) and Th2 cells, respectively. Consistent with their ability to make IL-10, both CD25(+) and CD25(-)CD4(+) T cells from infected mice were able, when stimulated with egg Ag, to suppress IL-12 production by CD40 agonist-stimulated dendritic cells. Additionally, in adoptive transfer experiments, both CD4(+) subpopulations of cells were able to partially inhibit the development of Th1 responses in egg-immunized IL-10(-/-) mice. The relationship of Treg cells in infected mice to natural Treg cells was strongly suggested by the ability of CD25(+)CD4(+) cells from naive mice to inhibit Th1 response development when transferred into egg-immunized or infected IL-10(-/-) mice. The data suggest that natural Treg cells and, to a lesser extent, Th2 cells play roles in suppressing Th1 responses and ensuring Th2 polarization during schistosomiasis.
McKee
Amy S
AS
Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104, USA.
Pearce
Edward J
EJ
D000818:Animals; D000941:Antigens / Q000276:immunology; D019013:CD40 Antigens / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D051379:Mice; D010063:Ovum / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D012550:Schistosoma mansoni / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000941:Antigens; D019013:CD40 Antigens; D015375:Receptors, Interleukin-2; D016753:Interleukin-10; D018664:Interleukin-12