Melanocyte-specific CD49a⁺ CD8⁺ T cells in vitiligo lesion potentiate to maintain activity during systemic steroid...

Vitiligo is a common depigmenting skin disease that is often difficult to treat. Even if repigmentation is achieved by treatment, recurrence in the same lesion is often found within a year after stopping treatment. As a background of these issues, a subset of CD8⁺ T cells that recognize melanocyte-specific antigens or CD49a⁺ tissue-resident memory T cells that reside in the vitiligo lesion are thought to be involved. We investigated the MHC class I-restricted tyrosinase pentamer-positive CD8⁺ skin T cells in a progressive generalized vitiligo patient with HLA-A*02:01 who showed resistance to intravenous methylprednisolone pulse therapy. We found that HLA-A*02:01-restricted tyrosinase pentamer-positive CD8⁺ T cells remained in the lesions after the treatment and expressed IFN-γ and granzyme B. Interestingly, the expression of these cytokines in the pentamer-negative CD8⁺ T cells was decreased after intravenous methylprednisolone pulse therapy. These findings suggest that, in vitiligo patients, melanocyte-specific CD49a⁺ CD8⁺ T cells are in a potent activation state that is uncontrolled despite systemic immunosuppressive treatment, which may contribute to treatment resistance and local recurrence.