Development of autoimmune vitiligo in pmel-1 CTLA-4^–/– mice is a result of qualitative rather than quantitative improvements in pmel-1 CD8⁺ T cells. (A) Quantitative analysis of CD8⁺ splenocytes in pmel-1 CTLA^+/+ and pmel-1 CTLA-4^–/– mice. Pmel-1 CTLA-4^–/– mice have significantly fewer CD8⁺ T cells compared with pmel-1 mice (P < .001). (B) Pmel-1 CTLA-4^–/– CD8⁺ T cells exhibit an activated phenotype. Flow cytometry for CD44 expression on CD8⁺ splenocytes from pmel-1 CTLA^+/+ and pmel-1 CTLA-4^–/– mice. Results are shown after gating for CD8. (C) Pmel-1 CTLA-4^–/– CD8⁺ T cells possess enhanced effector functions. Splenocytes from pmel-1 CTLA^+/+ and pmel-1 CTLA-4^–/– mice were enriched for CD8⁺ T cells and cocultured in the presence of gp100-pulsed, irradiated, T-cell–depleted splenocytes. Irradiated, unpulsed, T-cell–depleted splenocytes were used as controls. Pmel-1 CTLA-4^–/– CD8⁺ T cells release significantly greater amounts of IFN-γ (P < .001). (A, C) Values represent mean ± SEM.