title: Decrease of Foxp3+ Treg cell number and acquisition of effector cell phenotype during lethal infection.
abstract: Using a model of lethal oral infection with Toxoplasma gondii, we examined the fate of both induced and natural regulatory T (Treg) cells in the face of strong inflammatory responses occurring in a tolerogenic-prone environment. We found that during highly T helper 1 (Th1) cell-polarized mucosal immune responses, Treg cell numbers collapsed via multiple pathways, including blockade of Treg cell induction and disruption of endogenous Treg cell homeostasis. In particular, shutdown of interleukin 2 (IL-2) in the highly Th1 cell-polarized environment triggered by infection directly contributes to Treg cell incapacity to suppress effector responses and eventually leads to immunopathogenesis. Furthermore, we found that environmental cues provided by both local dendritic cells and effector T cells can induce the expression of T-bet transcription factor and IFN-gamma by Treg cells. These data reveal a mechanism for Th1 cell pathogenicity that extends beyond their proinflammatory program to limit Treg cell survival.
authors.affiliation: Mucosal Immunology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Oldenhove
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bouladoux
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Wohlfert
authors.forename: Jason A
authors.initials: JA
authors.lastname: Hall
authors.forename: David
authors.initials: D
authors.lastname: Chou
authors.forename: Liliane
authors.initials: L
authors.lastname: Dos Santos
authors.forename: Shaun
authors.initials: S
authors.lastname: O'Brien
authors.forename: Rebecca
authors.initials: R
authors.lastname: Blank
authors.forename: Erika
authors.initials: E
authors.lastname: Lamb
authors.forename: Sundar
authors.initials: S
authors.lastname: Natarajan
authors.forename: Robin
authors.initials: R
authors.lastname: Kastenmayer
authors.forename: Christopher
authors.initials: C
authors.lastname: Hunter
authors.forename: Michael E
authors.initials: ME
authors.lastname: Grigg
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Belkaid
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014122:Toxoplasma; D014123:Toxoplasmosis / Q000276:immunology
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2