title: Helios defines T cells being driven to tolerance in the periphery and thymus.
abstract: The expression of the Ikaros transcription factor family member, Helios, has been shown to be associated with T-cell tolerance in both the thymus and the periphery. To better understand the importance of Helios in tolerance pathways, we have examined the expression of Helios in TCR-transgenic T cells specific for the gastric H(+) /K(+) ATPase, the autoantigen target in autoimmune gastritis. Analysis of H(+) /K(+) ATPase-specific T cells in mice with different patterns of H(+) /K(+) ATPase expression revealed that, in addition to the expression of Helios in CD4(+) Foxp3(+) regulatory T (Treg) cells, Helios is expressed by a large proportion of CD4(+) Foxp3(-) T cells in both the thymus and the paragastric lymph node (PgLN), which drains the stomach. In the thymus, Helios was expressed by H(+) /K(+) ATPase-specific thymocytes that were undergoing negative selection. In the periphery, Helios was expressed in H(+) /K(+) ATPase-specific CD4(+) T cells following H(+) /K(+) ATPase presentation and was more highly expressed when T-cell activation occurred in the absence of inflammation. Analysis of purified H(+) /K(+) ATPase-specific CD4(+) Foxp3(-) Helios(+) T cells demonstrated that they were functionally anergic. These results demonstrate that Helios is expressed by thymic and peripheral T cells that are being driven to tolerance in response to a genuine autoantigen.
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Australia.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Ross
authors.forename: Dorothée
authors.initials: D
authors.lastname: Bourges
authors.forename: Thea V
authors.initials: TV
authors.lastname: Hogan
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gleeson
authors.forename: Ian R
authors.initials: IR
authors.lastname: van Driel
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004268:DNA-Binding Proteins / Q000502:physiology*; D051858:Forkhead Transcription Factors / Q000032:analysis; D005756:Gastritis / Q000276:immunology; D017506:H(+)-K(+)-Exchanging ATPase / Q000502:physiology; D007108:Immune Tolerance; D051379:Mice; D008807:Mice, Inbred BALB C; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D014157:Transcription Factors; C491746:Zfpn1a2 protein, mouse; D017506:H(+)-K(+)-Exchanging ATPase
keywords: Autoimmune gastritis; Helios; T-cell anergy; T-cell tolerance; Treg cells