Fig. 8.

Depletion of CD25⁺ regulatory T (Treg) cells reduces the inhibitory effect of FTY720 on the development of autoimmune arthritis and restores the type II collagen (CII)-specific T-cell response. Mice were immunized with CII on day 0 and split into four groups for treatment: (1) FTY720 + anti-CD25 antibody (Ab), (2) vehicle + anti-CD25 antibody, (3) FTY720 + control antibody (MOPC 167), and (4) vehicle + control antibody. Two days before immunization with CII, mice were treated with 250 μg of antibody (anti-CD25 or control), and antibody treatments were continued for 3 weeks with one treatment per week. a Representative data show that anti-CD25 treatment in the Treg cell population significantly depleted the CD25⁺Foxp3⁺ population in the peripheral blood and lymph nodes, and also significantly reduced the number of Foxp3⁺ cells in the lymph nodes. Starting at the time of immunization, mice were treated with FTY720, and treatment was continued three times per week for a total of nine doses. b Mice were scored three times per week for arthritis starting on day 18 after immunization. Data shown were derived from two separate experiments and normalized to the first day of disease onset for each experiment. The asterisks indicate statistically significant differences in arthritis incidence between the FTY720 + anti-CD25 group and the FTY720 + control Ab group in the study (p < 0.04 by χ² test). c CII-specific proliferative response of T cells from the mice presented in (b). On day 17 after immunization, cells from draining lymph nodes were placed in culture and restimulated with the CII_257–274 peptide. Proliferation was measured by [³H]thymidine incorporation, and data are representative of two experiments. Error bars indicate standard deviation