Compromised melanocyte survival due to decreased suppression of CD4+ & CD8+ resident memory T cells by impaired TRM-regulatory T cells in generalized vitiligo patients

Regulatory T cells (Tregs) are involved in the suppression of activated T cells in generalized vitiligo (GV). The study was aimed to investigate resident memory (TRM)-Tregs and antigen-specific Tregs' numbers and functional defects in 25 GV patients and 20 controls. CD4(+) & CD8(+) TRM cell proliferation was assessed by BrDU assay; production of IL-10, TGF-beta, IFN-gamma, perforin and granzyme B were assessed by ELISA and enumeration of TRM cells was done by flowcytometry. GV patients showed significantly increased frequency and absolute count of CD4(+) & CD8(+) TRM cells in lesional (L), perilesional (PL) and non-lesional (NL) skin compared to controls (p = 0.0003, p = 0.0029 & p = 0.0115, respectively & p = 0.0003, p = 0.003 & p = 0.086, respectively). Whereas, TRM-Treg (p < 0.0001 & p = 0.0015) and antigen-specific Tregs (p = 0.0014 & p = 0.003) exhibited significantly decreased frequency and absolute counts in L & PL skin. GV patients showed reduced suppression of CD8(+) & CD4(+) TRM cells (with increased IFN-gamma, perforin & granzyme B) and decreased TRM-Tregs and antigen-specific Tregs (with decreased IL-10 & TGF-beta production) and reduced proliferation of SK-Mel-28 cells in co-culture systems. Immunohistochemistry revealed increased expression of TRM stimulating cytokines: IL-15 & IL-17A and reduced expression of TGF-beta & IL-10 in L, PL, NL skins compared to controls. These results for the first time suggest that decreased and impaired TRM-Tregs and antigen-specific Tregs are unable to suppress CD4(+) & CD8(+) TRMs' cytotoxic function and their proliferation due to decrease production of immunosuppressive cytokines (IL-10 & TGF-beta) and increased production of TRM based IFN-gamma, perforin and granzyme B production, thus compromising the melanocyte survival in GV.

Automated summary

This study found that there are defects in the numbers and functional of TRM-Tregs and antigen-specific Tregs in patients with generalized vitiligo(GV). These defects result in the inability to suppress the cytotoxic function and proliferation of CD4(+) and CD8(+) TRM cells, compromising the survival of melanocytes.