Treatment of anti-CD3-activated peripheral RA memory CD4+ T cells with recombinant PD-L1-Fc reduced proliferation at the same level as healthy donor CD4+ T cells, demonstrating that even though the PD-1 pathway is down-modulated in RA, the downstream components of the pathway are intact and responsive to signaling via its natural ligand (Fig 3C). This evidence concerns the gene CD274 and rheumatoid arthritis.