Immune control of functional memory CD8 T cells in normal-appearing vitiligo skin

Emerging evidence demonstrates that self-reactive CD8⁺ T resident memory cells (T_RM cells) may already populate the never-lesional (NL) skin of patients with chronic inflammatory conditions, including vitiligo. However, their functional activity and regulation remain unknown. By combining cellular and transcriptomic approaches, we show that common CD8⁺ T cell clusters with a similar transcriptional profile infiltrate NL and peri-lesional (PL) skin of patients with vitiligo. Pathways related to immune activation were more active in T cells from PL skin, while those related to immune regulation were enriched in NL skin T cells, also evidenced by the stronger infiltration of regulatory T cells and the higher expression of programmed cell death protein 1 (PD-1) by CD8⁺ T cells in NL skin. Treatment of patients with baricitinib led to an increase in regulatory T cells and CD8⁺ T cells expressing PD-1 in repigmented skin. These findings suggest that functional T cells populate pigmented skin in vitiligo and highlight the importance of regulatory mechanisms to restrain their activation and prevent depigmentation.