title: Transient depletion of CD4+ CD25+ regulatory T cells results in multiple autoimmune diseases in wild-type and B-cell-deficient NOD mice.
abstract: Approximately 80% of female wild-type non-obese diabetic (WT NOD) mice spontaneously develop diabetes, whereas B-cell-deficient (B(-/-)) NOD mice are resistant to diabetes. B(-/-) mice are also resistant to other spontaneous and experimentally induced autoimmune diseases, including arthritis, systemic lupus erythematosus, Sjögren syndrome and thyroiditis. Under normal conditions, activation of self-reactive T cells in the periphery is limited by CD4(+) CD25(+) natural regulatory T (Treg) cells. B(-/-) NOD.H-2h4 mice, normally resistant to spontaneous autoimmune thyroiditis (SAT), develop SAT when Treg cells are depleted, suggesting that Treg cells are preferentially activated when autoantigen is initially presented by non-B-cell antigen-presenting cells. To test the hypothesis that increased Treg cell activity in B(-/-) mice contributes to their resistance to other autoimmune diseases, WT and B(-/-) NOD mice were given anti-CD25 to transiently deplete CD4(+) CD25(+) Treg cells. The WT and B(-/-) NOD mice given anti-CD25 developed diabetes much earlier than WT mice given rat IgG, whereas rat IgG-treated B(-/-) mice did not develop diabetes. Treg-cell-depleted mice had increased lymphocyte infiltration of the pancreas, salivary glands and thyroid compared with controls given rat IgG. These results are consistent with the hypothesis that resistance of B-cell-deficient NOD mice to several autoimmune diseases is due to the activity of Treg cells.
authors.affiliation: Department of Medicine, University of Missouri School of Medicine, Columbia, MO, USA.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Ellis
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Wan
authors.forename: Helen
authors.initials: H
authors.lastname: Braley-Mullen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D001168:Arthritis / Q000235:genetics / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D016688:Mice, Inbred NOD; D051381:Rats; D012469:Salivary Glands / Q000276:immunology / Q000378:metabolism; D012859:Sjogren's Syndrome / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013961:Thyroid Gland / Q000276:immunology / Q000378:metabolism; D013967:Thyroiditis, Autoimmune / Q000235:genetics / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D001324:Autoantigens; D007074:Immunoglobulin G; D053645:Interleukin-2 Receptor alpha Subunit