Increased frequencies of CD4+CD28− expressing CD161 and CD57 in patients with active RA have been demonstrated [21], [36]–[38], and CD4+CD161+ T cells preferentially accumulated at the outer edge of lymphoid aggregates [38], while CD57 expression may render cells more susceptible to activation-induced cell death by apoptosis [39]. Here, CD28 is linked to rheumatoid arthritis.