We demonstrated that neutralizing multiple cytokines, including IL-6, IL-10, IL-12, IL-23, IFNαβR, IFNβ, IFNγ, and TNF in RA synovial fluid and TCR-stimulated T cells, returns the expression of IRs, such as PD-1, TIM-3, LAG-3, and CD28, to TCR-only stimulation levels. Here, CD28 is linked to rheumatoid arthritis.