Figure 8.
Development of arthritis and other autoimmune diseases in Dox-low Tet-on ZAP mice. (A and B) Percent survival of Tet-on ZAP mice treated with Dox 2.0 (Dox-high) or Dox 0.5 (Dox-low) food. Percent survival in A and body weight changes in B (n = 14 and 13, respectively). Body weight changes of BALB/c and ZAP-70−/− mice (n = 5 each) are also shown in B. (C) Joint swelling of a forepaw and a hind paw in Dox 0.5 Tet-on ZAP or BALB/c mice. Scale bar: 3 mm. (D) Incidence (left) and severity (right) of arthritis in Tet-on ZAP mice treated with Dox 2.0 or 0.5 food for 10 wk. (E–G) Incidences of histologically evident autoimmune diseases (E), histology of affected organs (F), and disease scores (G), in Dox 0.5 or 2.0 treated Tet-on ZAP or BALB/c mice. Scale bar: 200 μm. (H) Serum titers of RF and anti-CCP and serum concentrations of IgG and IgE in Tet-on ZAP mice treated with Dox 2.0 or 0.5 food for 10 wk, untreated (Dox[−]) ZAP-70−/−, or normal BALB/c mice. (I) FACS staining of indicated molecules for splenic Foxp3− and Foxp3+CD4+ T cells in Tet-on ZAP mice Dox-treated for 10 wk. Percentage within gate and MFIs (in parentheses) are indicated. (J) IL-17A and IFN-γ intracellular staining of CD4+ T cells in Dox-treated Tet-on ZAP mice as in I. Representative of three independent experiments. Two-tailed unpaired Student’s t test in D, G, and H, logrank test in A. Mean ± SD in B, D, and G.