title: Transient Treg-cell depletion in adult mice results in persistent self-reactive CD4(+) T-cell responses.
abstract: Depletion of Foxp3(+) CD4(+) regulatory T cells (Treg) in adults results in chronic inflammation and autoimmune disease. However, the impact of transient Treg-cell depletion on self-reactive responses is poorly defined. Here, we studied the effect of transient depletion of Treg cells on CD4(+) T-cell responses to endogenous self-antigens. Short-term ablation of Treg cells in mice resulted in rapid activation of CD4(+) T cells, increased percentage of IFN-γ(+) and Th17 cells in lymphoid organs, and development of autoimmune gastritis. To track self-reactive responses, we analyzed the activation of naïve gastric-specific CD4(+) T cells. There was a dramatic increase in proliferation and acquisition of effector function of gastric-specific T cells in the stomach draining LNs of Treg-cell-depleted mice, compared with untreated mice, either during Treg-cell depletion or after Treg-cell reconstitution. Moreover, the hyperproliferation of gastric-specific T cells in the Treg-cell-ablated mice was predominantly antigen-dependent. Transient depletion of Treg cells resulted in a shift in the ratio of peripheral:thymic Treg cells in the reemerged Treg-cell population, indicating an altered composition of Treg cells. These findings indicate that transient Treg-cell depletion results in ongoing antigen-driven self-reactive T-cell responses and emphasize the continual requirement for an intact Treg-cell population.
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Sofia N
authors.initials: SN
authors.lastname: Nyström
authors.forename: Dorothée
authors.initials: D
authors.lastname: Bourges
authors.forename: Sarah
authors.initials: S
authors.lastname: Garry
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Ross
authors.forename: Ian R
authors.initials: IR
authors.lastname: van Driel
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gleeson
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity; D049109:Cell Proliferation; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D013270:Stomach / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
chemical_list: D001324:Autoantigens; D007371:Interferon-gamma
keywords: Autoimmune gastritis; Foxp3; Gastric H/K ATPase; Immune homeostasis; Regulatory T (Treg) cells