Adoptive Cell Therapy of Induced Regulatory T Cells Expanded by Tolerogenic Dendritic Cells on Murine Autoimmune Arthritis.

OBJECTIVE

Tolerogenic dendritic cells (tDCs) can expand TGF--induced regulatory T cells (iTregs); however, the therapeutic utility of these expanded iTregs in autoimmune diseases remains unknown. We sought to determine the properties of iTregs expanded by mature tolerogenic dendritic cells (iTreg) in vitro and explore their potential to ameliorate collagen-induced arthritis (CIA) in a mouse model.

METHODS

After induction by TGF- and expansion by mature tDCs (mtDCs), the phenotype and proliferation of iTreg were assessed by flow cytometry. The ability of iTregs and iTreg to inhibit CD4 T cell proliferation and suppress Th17 cell differentiation was compared. Following adoptive transfer of iTregs and iTreg to mice with CIA, the clinical and histopathologic scores, serum levels of IFN-, TNF-, IL-17, IL-6, IL-10, TGF- and anti-CII antibodies, and the distribution of the CD4 Th subset were assessed.

RESULTS

Compared with iTregs, iTreg expressed higher levels of Foxp3 and suppressed CD4 T cell proliferation and Th17 cell differentiation to a greater extent. In vivo, iTreg reduced the severity and progression of CIA more significantly than iTregs, which was associated with a modulated inflammatory cytokine profile, reduced anti-CII IgG levels, and polarized Treg/Th17 balance.

CONCLUSION

This study highlights the potential therapeutic utility of iTreg in autoimmune arthritis and should facilitate the future design of iTreg immunotherapeutic strategies.