Exponentially decreasing exposure of antigen generates anti-inflammatory T-cell responses

Abstract

AbstractRheumatoid Arthritis (RA) is a chronic debilitating disease characterized by auto-immune reaction towards self-antigen such as collagen type II. In this study, we investigated the impact of exponentially decreasing levels of antigen exposure on pro-inflammatory T cell responses in the collagen-induced arthritis (CIA) mouse model. Using a controlled delivery experimental approach, we manipulated the collagen type II (CII) antigen concentration presented to the immune system. We observed that exponentially decreasing levels of antigen generated reduced pro-inflammatory T cell responses in secondary lymphoid organs in mice suffering from RA. Specifically, untreated mice exhibited robust pro-inflammatory T cell activation and increased paw inflammation, whereas, mice exposed to exponentially decreasing concentrations of CII demonstrated significantly reduced pro-inflammatory T cell responses, exhibited lower levels of paw inflammation, and decreased arthritis scores in right rear paw. The data also demonstrate that the decreasing antigen levels promoted the induction of regulatory T cells (Tregs), which play a crucial role in maintaining immune tolerance and suppressing excessive inflammatory responses. Our findings highlight the importance of antigen concentration in modulating pro-inflammatory T cell responses in the CIA model. These results provide valuable insights into the potential therapeutic strategies that target antigen presentation to regulate immune responses and mitigate inflammation in rheumatoid arthritis and other autoimmune diseases. Further investigations are warranted to elucidate the specific mechanisms underlying the antigen concentration-dependent modulation of T cell responses and to explore the translational potential of this approach for the development of novel therapeutic interventions in autoimmune disorders.