Figure 6

ICOS co-stimulated peripheral blood T cells in active SLE enhanced IgG anti-dsDNA antibody production by autologous B cells. Peripheral blood T cells and B cells were isolated from eight patients with active SLE, reconstituted at a 1:1 ratio and cultured in the presence of anti-CD3 mAb plus JTA009 (ICOS co-stimulation), anti-CD3 mAb plus anti-CD28 mAb (CD28 co-stimulation), anti-CD3 mAb plus JMAb23 (anti-CD3), or without stimulation for 7 days. IgG anti-dsDNA antibody and total IgG were determined by ELISA. The mean ± SD production of IgG anti-dsDNA antibody and total IgG, respectively, were as follows: anti-CD3 mAb plus JMAb23, 45.4 ± 64.4 U/ml and 274± 141 ng/ml; ICOS co-stimulation, 98.3 ± 118 U/ml and 475 ± 297 ng/ml; CD28 co-stimulation, 46.1 ± 64.1 U/ml and 734 ± 694 ng/ml; and without stimuli, 22.0 ± 29.7 U/ml and 216 ± 180 ng/ml. Co-stimulation indices for (a) IgG anti-dsDNA antibody and (b) total IgG were calculated as follows: the IgG anti-dsDNA antibody or total IgG production with co-stimulation/the IgG anti-dsDNA antibody or total IgG production with anti-CD3 mAb plus JMAb23. Differences between stimuli were evaluated using Wilcoxon rank sum test. Ab, antibody; ds, double stranded; ICOS, inducible co-stimulator; SD, standard deviation; SLE, systemic lupus erythematosus.