TY - JOUR
T1 - Transient depletion of CD4+ CD25+ regulatory T cells results in multiple autoimmune diseases in wild-type and B-cell-deficient NOD mice
AU - Ellis, Jason S.
AU - Wan, Xiaoxiao
AU - Braley-Mullen, Helen
PY - 2013/6
Y1 - 2013/6
N2 - 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.
AB - 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.
KW - Autoimmunity
KW - Diabetes
KW - Regulatory T cell
KW - Salivary gland
KW - Thyroid
UR - http://www.scopus.com/inward/record.url?scp=84876789733&partnerID=8YFLogxK
U2 - 10.1111/imm.12065
DO - 10.1111/imm.12065
M3 - Article
C2 - 23293979
AN - SCOPUS:84876789733
SN - 0019-2805
VL - 139
SP - 179
EP - 186
JO - Immunology
JF - Immunology
IS - 2
ER -