title: Requirement for diverse TCR specificities determines regulatory T cell activity in a mouse model of autoimmune arthritis.
abstract: CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) are required to restrain the immune system from mounting an autoaggressive systemic inflammatory response, but why their activity can prevent (or allow) organ-specific autoimmunity remains poorly understood. We have examined how TCR specificity contributes to Treg activity using a mouse model of spontaneous autoimmune arthritis, in which CD4(+) T cells expressing a clonotypic TCR induce disease by an IL-17-dependent mechanism. Administration of polyclonal Tregs suppressed Th17 cell formation and prevented arthritis development; notably, Tregs expressing the clonotypic TCR did not. These clonotypic Tregs exerted Ag-specific suppression of effector CD4(+) T cells using the clonotypic TCR in vivo, but failed to mediate bystander suppression and did not prevent Th17 cells using nonclonotypic TCRs from accumulating in joint-draining lymph nodes of arthritic mice. These studies indicate that the availability of Tregs with diverse TCR specificities can be crucial to their activity in autoimmune arthritis.
authors.affiliation: The Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Oh
authors.forename: Malinda
authors.initials: M
authors.lastname: Aitken
authors.forename: Donald M
authors.initials: DM
authors.lastname: Simons
authors.forename: Alissa
authors.initials: A
authors.lastname: Basehoar
authors.forename: Victoria
authors.initials: V
authors.lastname: Garcia
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kropf
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Caton
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D020381:Interleukin-17 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009928:Organ Specificity / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
chemical_list: D020381:Interleukin-17; D011948:Receptors, Antigen, T-Cell