TNF and rheumatoid arthritis: Arthritis develops due to the lack of immune regulation resulting from CTLA-4 and PD-1/PD-L1 suppression, leading to unchecked T-cell responses, elevation of IL-17 and TNF-α, and infiltration of effector memory CD8+ T-cells into the synovium, which differentiates it from autoantibody-mediated RA.