Fig. 4
Therapeutic activity of PBC-relevant pMHCII-NPs can be suppressed by IL-10 and TGFβ blockade. a Percentages of tetramer+CD4+ T cells in blood and lymphoid organs of NOD.c3c4.scid hosts reconstituted with whole splenocytes from untreated NOD.c3c4 donors a day after transfusion with splenic CD4+ T-cells from untreated or PDC166–181/IAg7-NP-treated NOD.c3c4 mice. The hosts were either left untreated or were treated with PDC166–181/IAg7-NPs. b Representative FACS staining histograms (left) and average mean fluorescence intensity values for TR1 markers on tetramer+CD4+ vs. tetramer−CD4+ T-cells (right) of the hosts treated with PDC166–181/IAg7-NPs. c and d Macroscopic scores and liver weights (c) and microscopic scores (d) of the mice studied in a. Data in a–d correspond to means ± SEM, were compared with Mann–Whitney U, and correspond to n = 9 (blue in c) or 7 (blue in d), 5 (red in a, c, and d), and 5 mice (green in a, c, d)/treatment group, respectively. e Percentages of tetramer+ CD4+ T-cells in mice treated with pMHCII-NPs and rat-IgG (control) or blocking rat mAbs against mouse IL-10 or TGFβ. f–g Macroscopic (f) and microscopic (g) scores of the mice studied in a. Data in e–g correspond to n = 5, 3–4 and 4 mice/treatment group, respectively. h Macroscopic scores, liver weights, and microscopic scores of NOD.c3c4.scid hosts reconstituted with whole splenocytes from untreated NOD.c3c4 donors a day after transfusion of the hosts with: FACS-sorted splenic/PCLN-derived tetramer+CD4+ T-cells from PDC166–181/IAg7-NP-treated NOD.c3c4 mice; purified PCLN B-cells from PDC166–181/IAg7-NP-treated NOD.c3c4 mice; FACS-sorted splenic/PLN-derived tetramer+CD4+ T-cells from BDC2.5mi/IAg7-NP-treated NOD; or purified PLN B-cells from BDC2.5mi/IAg7-NP-treated NOD mice. Data in h correspond to n = 5/group (red, blue and yellow) or n = 4/group (orange and cyanine). Data in a–h correspond to mean ± SEM. P values were calculated via Mann–Whitney U
