TCL18, a CD45RO−CD45RA−CCR7− CD4-SP cluster characterized by CTLA-4low+, ICOSlow+, Faslow+, CD28+, CD25low+, CD127−, and CCR4+, mirrored the attributes of nonregulatory, proinflammatory cytokine-secreting cells (human Treg fraction III (34) and positively correlated with SDAI, CRP, and MMP-3 levels, suggesting associations with markers of RA disease activity. The gene discussed is CD28; the disease is rheumatoid arthritis.