title: Inhibition of follicular T-helper cells by CD8(+) regulatory T cells is essential for self tolerance.
abstract: The ability to produce vigorous immune responses that spare self tissues and organs depends on the elimination of autoreactive T and B cells. However, purging of immature and mature self-reactive T and B cells is incomplete and may also require the involvement of cells programmed to suppress immune responses. Regulatory T cells (T(reg)) belonging to the CD4(+) T-cell subset may have a role in preventing untoward inflammatory responses, but T-cell subsets programmed to inhibit the development of autoantibody formation and systemic-lupus-erythematosus-like disease have not yet been defined. Here we delineate a CD8(+) regulatory T-cell lineage that is essential for the maintenance of self tolerance and prevention of murine autoimmune disease. Genetic disruption of the inhibitory interaction between these CD8(+) T cells and their target Qa-1(+) follicular T-helper cells results in the development of a lethal systemic-lupus-erythematosus-like autoimmune disease. These findings define a sublineage of CD8 T cells programmed to suppress rather than activate immunity that represents an essential regulatory element of the immune response and a guarantor of self tolerance.
authors.affiliation: Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA.
authors.forename: Hye-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Bert
authors.initials: B
authors.lastname: Verbinnen
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Tang
authors.forename: Linrong
authors.initials: L
authors.lastname: Lu
authors.forename: Harvey
authors.initials: H
authors.lastname: Cantor
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D000915:Antibody Affinity / Q000276:immunology; D000941:Antigens / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D019070:Cell Lineage; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D051379:Mice; D018448:Models, Immunological; D009154:Mutation; D017634:Self Tolerance / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology
chemical_list: D000906:Antibodies; D000941:Antigens; D001323:Autoantibodies; D015395:Histocompatibility Antigens Class I; D018960:Hyaluronan Receptors; D007074:Immunoglobulin G; C032907:Q surface antigens