Here, we demonstrate that antigen presentation by RA FLS results in hyporesponsive T cells, characterized by limited expression of functional activation molecules CD25 (IL-2RA) and HLA-DR, reduced effector cytokine production (IL-2 and IFN-γ), and suppressed proliferation compared with T cells activated by professional APCs. The gene discussed is IFNG; the disease is rheumatoid arthritis.