(A) Representative histograms of three independent experiments (left
panel) depicting Celltrace Violet (CTV) dilution profile of responder
CD4+ T cells cultured alone (thin grey line) or with either
wild-type Treg cells (dashed grey line) or M370I Treg cells (black line) at a
ratio of 1:8 (Treg cells:responders). Quantification (right panel) of the
in vitro suppression assay by the division index at
different Treg cell:responder ratios. (B) Weight loss (as a percentage of
starting weight) over time after injection of naïve CD4+ T
cells into immunodeficient Rag1−/−
mice followed by WT or M370I Treg cells three weeks later. At the time of Treg
injections, mice were randomly assigned to the three experimental groups. Error
bars depict ±SEM, Two-way ANOVA test: naïve T cells/naiïve
T cells + WT Tregs; week 7 (P < 0.001), naïve T
cells/naiïve T cells + M370I Tregs; week 7 (P <
0.001). (C) Phenotypic analysis of Treg cells from LNs or spleen from wild-type
(dashed grey line) and M370I littermates (black line) by staining for indicated
proteins at 6-12 weeks of age. (D) Representative intracellular staining for
IL-10 after PMA-ionomycin activation of splenic Treg cells from wild-type and
M370I littermates at 6-12 weeks of age. (E) Flow cytometric analysis for
proliferation (Ki67) and activation (CD44, CD62L and CCR7) markers on Treg cells
from LNs and spleen from wild-type and M370I littermates. Expression and
quantification from mice analyzed between 6 and 12 weeks of age. (F)
Representative histograms for PD-1 and ICOS expression on Treg cells from LNs
and spleen from wild-type and M370I littermates at 6-12 weeks of age (G)
Representative flow cytometric analysis (left panel) and quantification (right
panel) of Tfr cells in spleen and peyer’s patches from 6-12-week-old
wild-type and M370I littermates. All data points reflect individual biological
replicates (error bars depict ±SD, unless otherwise stated).