Journal
NATURE
Volume 490, Issue 7418, Pages 102-U119Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature11462
Keywords
-
Categories
Funding
- NIH-NIAID [R01AI087830, R01AI100934]
- NIH-NIDDK [F30DK084674]
- Burroughs Wellcome Fund
Ask authors/readers for more resources
Pregnancy is an intricately orchestrated process where immune effector cells with fetal specificity are selectively silenced. This requires the sustained expansion of immune-suppressive maternal FOXP3(+) regulatory T cells (T-reg cells), because even transient partial ablation triggers fetal-specific effector T-cell activation and pregnancy loss(1,2). In turn, many idiopathic pregnancy complications proposed to originate from disrupted fetal tolerance are associated with blunted maternal T-reg expansion(3-5). Importantly, however, the antigen specificity and cellular origin of maternal Treg cells that accumulate during gestation remain incompletely defined. Here we show that pregnancy selectively stimulates the accumulation of maternal FOXP3(+) CD4 cells with fetal specificity using tetramer-based enrichment that allows the identification of rare endogenous T cells(6). Interestingly, after delivery, fetal-specific T-reg cells persist at elevated levels, maintain tolerance to pre-existing fetal antigen, and rapidly re-accumulate during subsequent pregnancy. The accelerated expansion of T-reg cells during secondary pregnancy was driven almost exclusively by proliferation of fetal-specific FOXP3(+) cells retained from prior pregnancy, whereas induced FOXP3 expression and proliferation of pre-existing FOXP3(+) cells each contribute to T-reg expansion during primary pregnancy. Furthermore, fetal resorption in secondary compared with primary pregnancy becomes more resilient to partial maternal FOXP3(+) cell ablation. Thus, pregnancy imprints FOXP3(+) CD4 cells that sustain protective regulatory memory to fetal antigen. We anticipate that these findings will spark further investigation on maternal regulatory T-cell specificity that unlocks new strategies for improving pregnancy outcomes and novel approaches for therapeutically exploiting T-reg cell memory.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available