Continuous exposure to antigens in inflammatory environments can result in dampening of particular cellular functions such as proliferation or cytokine release, however the enhanced expression of IL21 and CXCL13 indicates that not all functions within PD-1+ cells have been compromised and suggests that in the context of early RA examined here, these cells are contributing to disease pathogenesis. The gene discussed is IL21; the disease is rheumatoid arthritis.