title: Arthritogenic self-reactive CD4+ T cells acquire an FR4hiCD73hi anergic state in the presence of Foxp3+ regulatory T cells.
abstract: Rheumatoid arthritis develops in association with a defect in peripheral CD4(+) T cell homeostasis. T cell lymphopenia has also been shown to be a barrier to CD4(+) T cell clonal anergy induction. We therefore explored the relationship between clonal anergy induction and the avoidance of autoimmune arthritis by tracking the fate of glucose-6-phosphate isomerase (GPI)-reactive CD4(+) T cells in the setting of selective T cell lymphopenia. CD4(+) T cell recognition of self-GPI peptide/MHC class II complexes in normal murine hosts did not lead to arthritis and instead caused those T cells to develop a Folate receptor 4(hi)CD73(hi) anergic phenotype. In contrast, hosts selectively depleted of polyclonal Foxp3(+)CD4(+) regulatory T cells could not make GPI-specific CD4(+) T cells anergic and failed to control arthritis. This suggests that autoimmune arthritis develops in the setting of lymphopenia when Foxp3(+)CD4(+) regulatory T cells are insufficient to functionally inactivate all autoreactive CD4(+) T cells that encounter self-Ag.
authors: Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
authors: Ryan J
authors: RJ
authors: Martinez
authors: Na
authors: N
authors: Zhang
authors: Stephanie R
authors: SR
authors: Thomas
authors: Sarada L
authors: SL
authors: Nandiwada
authors: Marc K
authors: MK
authors: Jenkins
authors: Bryce A
authors: BA
authors: Binstadt
authors: Daniel L
authors: DL
authors: Mueller
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology*; D017635:Clonal Anergy / Q000235:genetics / Q000276:immunology*; D005956:Glucose-6-Phosphate Isomerase / Q000235:genetics / Q000276:immunology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D059470:Tetraspanins / Q000235:genetics / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; C504565:Cd37 protein, mouse; D011956:Receptors, Cell Surface; D059470:Tetraspanins; C543634:folate receptor 4, mouse; D005956:Glucose-6-Phosphate Isomerase