CD28 and rheumatoid arthritis: On the other hand, SEB alone was able to induce a significant IL-21 release in the monoculture of Th cells from RA patients, which could be explained by the abundant expression of TCR and CD28, as well as HLA-DR antigen, on these cells [42], which would increase the sensitivity to TCR-mediated signals, even in the absence of co-stimulation by B cells [43].