ICOS controls Foxp3(+) regulatory T-cell expansion, maintenance and IL-10 production during helminth infection

Stephen A Redpath, Nienke van der Werf, Ana M Cervera, Andrew S Macdonald, David Gray, Rick M Maizels, Matthew D Taylor

Research output: Contribution to journalArticlepeer-review

Abstract

Foxp3 regulatory T (Treg) cells are key immune regulators during helminth infections, and identifying the mechanisms governing their induction is of principal importance for the design of treatments for helminth infections, allergies and autoimmunity. Little is yet known regarding the co-stimulatory environment that favours the development of Foxp3 Treg-cell responses during helminth infections. As recent evidence implicates the co-stimulatory receptor ICOS in defining Foxp3 Treg-cell functions, we investigated the role of ICOS in helminth-induced Foxp3 Treg-cell responses. Infection of ICOS mice with Heligmosomoides polygyrus or Schistosoma mansoni led to a reduced expansion and maintenance of Foxp3 Treg cells. Moreover, during H. polygyrus infection, ICOS deficiency resulted in increased Foxp3 Treg-cell apoptosis, a Foxp3 Treg-cell specific impairment in IL-10 production, and a failure to mount putatively adaptive Helios Foxp3 Treg-cell responses within the intestinal lamina propria. Impaired lamina propria Foxp3 Treg-cell responses were associated with increased production of IL-4 and IL-13 by CD4 T cells, demonstrating that ICOS dominantly downregulates Type 2 responses at the infection site, sharply contrasting with its Type 2-promoting effects within lymphoid tissue. Thus, ICOS regulates Type 2 immunity in a tissue-specific manner, and plays a key role in driving Foxp3 Treg-cell expansion and function during helminth infections.
Original languageEnglish
Pages (from-to)705-715
Number of pages11
JournalEuropean Journal of Immunology
Volume43
Issue number3
DOIs
Publication statusPublished - 2013

Keywords

  • Co-stimulatory molecules
  • Immune regulation
  • Parasitology

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