Estrogen ameliorates antigen-induced arthritis (AIA) via estrogen receptor alpha (ERα). Total ERα-/- and wild-type (WT) littermates were treated with placebo or estrogen (E2) (0.83 μg/day) and induced with AIA. (A) Histological scoring of synovitis and joint destruction. The histological examination was performed by using a scale from 1 to 3: 1, mild; 2, moderate; and 3, severe. *P <0.05, **P <0.01, ***P <0.001 Mann-Whitney U test. (B) Representative images of joint histology. (C) Percentage of viable CD4+ Th (T helper) cells and CD8+ Tc (T cytotoxic) cells in the spleen. **P <0.01, Student t test. (D) In vitro proliferation of splenocytes, harvested from mice with AIA treated with placebo or E2 (0.83 μg/day), after stimulation with the T-cell mitogen concanavalin A (conA). Cell cultures were set in triplicates, and results are presented as proliferation index (median of count per minute in wells with conA minus the median of count per minute in control wells). *P <0.05, Student t test. Results are shown as mean ± standard error of the mean (n = 14-19).