Fig. 6
Effects of intermittent vs. continuous therapy. a and b Changes in the circulating frequency of tetramer+CD4+ T-cells in response to intermittent re-treatment (as a function of circulating tetramer+ T-cell levels). a shows profiles of one mouse, where the green arrows indicate the timing of individual doses and double arrowheads indicate that two doses were given in that particular week(s). Treatment was withdrawn at 24 weeks of age. Mice were monitored for persistence of tetramer+ cells in blood once every two weeks. When the percentages of tetramer+ cells fell below 50% of the original values, treatment was re-initiated and when the percentages of tetramer+ cells in blood recovered, treatment was withdrawn again. b shows the average values ± SEM corresponding to cohorts of NOD.c3c4 mice intermittently treated with PDC166–181/IAg7-NPs (n = 19) or left untreated (n = 16) after withdrawal of continued therapy (twice a week from 15 to 24 weeks of age). Data are from four experiments. c and d Percentage of tetramer+CD4+T-cells and mean fluorescence intensity staining for TR1 markers in tetramer+CD4+ T-cells from the mice studied in a and b. Data in c correspond to n = 12 pMHCII-NP-treated and 13 untreated mice/organ, respectively, from four experiments. Data in d correspond to n = 6 mice/group/organ. e–g Serum TBA and ALT levels (e; n = 10, 11, 8 and 7, from left to right, respectively), macroscopic (f; n = 14, 16, 19, and 8, from left to right, respectively) and microscopic (g; n = 15, 12, 7, and 8 from left to right, respectively) scores from mice treated intermittently (from 15 to 50 weeks of age), or continuously (twice a week from 24 to 38–44 weeks of age). Averaged data correspond the mean ± SEM. P values were compared via Mann–Whitney U (c–g) or two-way ANOVA (b)
