CD28 and rheumatoid arthritis: The best studied example is RA where increased replicative history is not only supported by the finding of telomeric erosion (Schonland et al., 2003; Fujii et al., 2009), but also by increased dilution of TCR excision circles (Koetz et al., 2000; Ponchel et al., 2002) and by repertoire contraction in TCR β-chain diversity within the naïve compartment (Wagner et al., 1998) and accumulation of terminally differentiated CD4 effector T cells that have lost the expression of CD28 (Schmidt et al., 1996a,b; Warrington et al., 2001).