The antigen-specific T cell vaccine reduces mature neutrophil accrued in the spleen to induce immune tolerance in rheumatoid arthritis

RA, an autoimmune disease characterized by debilitating pain and joint damage, poses challenges in current treatments due to their non-specific nature and potential for systemic side effects. This study introduces a novel therapeutic approach – Antigen-Specific T Cell Vaccine (AgTCV), targeting the root cause of RA by selectively suppressing autoantigen-specific cells without compromising overall immunity. Utilizing a citrullinated self-peptide derived from collagen II, we developed AgTCV through selective expansion and inactivation of autoreactive T cells. In vivo experiments using a collagen-induced arthritis (CIA) mouse model demonstrated the sustained efficacy of AgTCV, reducing inflammation, cartilage damage, and bone erosion. The vaccine also modulated immune responses, decreasing pro-inflammatory cytokines and pathogenic autoantibody levels. AgTCV's subcutaneous delivery showcased prolonged persistence, efficient recruitment in draining lymph nodes, and enhanced dendritic cell maturation at the injection site. Single-cell transcriptome analysis revealed dynamic changes induced by AgTCV, emphasizing the pivotal role of neutrophils in remodeling inflammatory tissue towards immune homeostasis. These findings propose AgTCV as a promising, cost-effective, and targeted immunotherapy for RA, with implications for broader applications in autoimmune disorders.