Transient depletion of CD4+ CD25+ regulatory T cells results in multiple autoimmune diseases in wild-type and B-cell-deficient NOD mice

Immunology. 2013 Jun;139(2):179-86. doi: 10.1111/imm.12065.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • Arthritis / genetics
  • Arthritis / immunology
  • Autoantigens / immunology
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology
  • Immunoglobulin G / immunology
  • Immunoglobulin G / pharmacology
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Lupus Erythematosus, Systemic / genetics
  • Lupus Erythematosus, Systemic / immunology
  • Lymphocyte Activation / immunology
  • Lymphocyte Depletion*
  • Mice
  • Mice, Inbred NOD
  • Rats
  • Salivary Glands / immunology
  • Salivary Glands / metabolism
  • Sjogren's Syndrome / genetics
  • Sjogren's Syndrome / immunology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Thyroid Gland / immunology
  • Thyroid Gland / metabolism
  • Thyroiditis, Autoimmune / genetics
  • Thyroiditis, Autoimmune / immunology


  • Antibodies, Monoclonal
  • Autoantigens
  • Immunoglobulin G
  • Interleukin-2 Receptor alpha Subunit