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Human CD4+ T cells

CD25 CD45RA

FOXP3 FOXP3
Thymus

nTregs
Ki-67 CD45RA CD25 high

CTLA-4 +

Non-Tregs eTregs

FOXP3
FOXP3

CD25

FOXP3
FIG 18.3 Expression of CD25 and Foxp3 Denotes Tregs in Mice and in Humans. In mice, between 5% and 10% of CD4 T cells
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express CD25, and among these, almost all are Foxp3 . In addition, a few Foxp3-expressing cells reside among CD4 CD25 T cells.
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−
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In the peripheral blood of humans, expression of surface marker CD25 is well correlated with intracellular FOXP3, especially when
the levels of CD25 and FOXP3 are high (top left). CD45RA and intracellular expression of FOXP3 enables the definition of three
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distinct subsets within FOXP3 CD4 T cells: CD45RA effector Treg cells with high expression of FOXP3 (blue box), CD45RA naïve
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Treg cells with low expression of FOXP3 (red box), and CD45RA non-Treg cells with low expression of FOXP3 (top right, purple
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box;). Effector FOXP3 high Treg cells correspond to actively proliferating Treg cells in vivo as they express Ki-67 (bottom left, purple
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low
box). The thymus produces CD45RA FOXP3 naïve Tregs as well as naïve CD45RA non-Treg cells. Upon antigenic stimulation,
naïve Tregs differentiate to CD45RA FOXP3 high effector Tregs, which are potently suppressive and capable of suppressing the prolifera-
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tion of other Tregs as well as non-Tregs in vitro (bottom right).