@article{smithlowlevel,
  abstract = {Helminth infection is frequently associated with the expansion of regulatory T cells (Tregs) and suppression of immune responses to bystander antigens. We show that infection of mice with the chronic gastrointestinal helminth Heligmosomoides polygyrus drives rapid polyclonal expansion of Foxp3+Helios+CD4+ thymic (t)Tregs in the lamina propria and mesenteric lymph nodes while Foxp3+Helios-CD4+ peripheral (p)Treg expand more slowly. Notably, in partially resistant BALB/c mice parasite survival positively correlates with Foxp3+Helios+CD4+ tTreg numbers. Boosting of Foxp3+Helios+CD4+ tTreg populations by administration of recombinant interleukin-2 (rIL-2):anti-IL-2 (IL-2C) complex increased worm persistence by diminishing type-2 responsiveness in vivo, including suppression of alternatively activated macrophage and granulomatous responses at the sites of infection. IL-2C also increased innate lymphoid cell (ILC) numbers, indicating that Treg functions dominate over ILC effects in this setting. Surprisingly, complete removal of Tregs in transgenic Foxp3-DTR mice also resulted in increased worm burdens, with [ldquo]immunological chaos[rdquo] evident in high levels of the pro-inflammatory cytokines IL-6 and interferon-[gamma]. In contrast, worm clearance could be induced by anti-CD25 antibody-mediated partial depletion of early Treg, alongside increased T helper type 2 responses and without incurring pathology. These findings highlight the overarching importance of the early Treg response to infection and the non-linear association between inflammation and the prevailing Treg frequency.},
  added-at = {2015-09-09T11:25:58.000+0200},
  author = {Smith, K A and Filbey, K J and Reynolds, L A and Hewitson, J P and Harcus, Y and Boon, L and Sparwasser, T and Hammerling, G and Maizels, R M},
  biburl = {https://www.bibsonomy.org/bibtex/25ccef7876f7ad84da7ea74891d598fa2/sparwasser},
  editor = {Immunol, Mucosal},
  interhash = {36e5e1793e8579d5a8426c90145763f8},
  intrahash = {5ccef7876f7ad84da7ea74891d598fa2},
  journal = {Mucosal Immunol},
  keywords = {sparwasser},
  number = 2,
  pages = {428-443},
  pubmedurl = {http://www.ncbi.nlm.nih.gov/pubmed/26286232},
  timestamp = {2016-04-06T12:38:24.000+0200},
  title = {Low-level regulatory T-cell activity is essential for functional type-2 effector immunity to expel gastrointestinal helminths},
  volume = 9,
  year = 2016
}