When the latter become activated, they begin to proliferate and secrete additional cytokines including IL-2, interferon-gamma (IFN-γ), TNF, and IL-4. It is under the effect of these T-cell-derived cytokines that additional cells become activated. B-cells become activated through interactions with T-cells and differentiate into antibody-forming plasma cells. These inflammatory cells mediate an immune response in genetically susceptible individuals to cause RA. This evidence concerns the gene IL4 and rheumatoid arthritis.