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Pregnancy Generates Sustained Maternal Anergy to Fetal Antigen

Immune-suppressing cells rapidly re-accumulate during subsequent pregnancies in mouse study

FRIDAY, Sept. 28 (HealthDay News) -- Pregnancy generates fetal-specific immune cells that suppress the immune response towards the fetus, which are rapidly re-accumulated in subsequent pregnancies, according to an experimental study published online Sept. 26 in Nature.

To establish the antigen specificity and cellular origin of maternal regulatory T cells that accumulate during gestation, Jared H. Rowe, Ph.D., from the University of Minnesota School of Medicine in Minneapolis, and colleagues impregnated female mice with strains of male mice expressing a surrogate fetal antigen.

The researchers found that maternal FOXP3-positive CD4 cells with fetal specificity selectively accumulated during pregnancy. The fetal-specific regulatory T cells persisted at elevated levels after delivery and remained tolerant to pre-existing fetal antigen. While induced FOXP3 expression and proliferation of pre-existing FOXP3-positive cells were the main contributors to regulatory T cell expansion during the primary pregnancy, proliferation of fetal-specific FOXP3-positive cells from the previous pregnancy was the main contributor to the rapid re-accumulation of regulatory T cells during subsequent pregnancies. In secondary versus primary pregnancies, fetal resorption became more resilient to partial maternal FOXP3-positive cell ablation.

"Together, these findings establish a model whereby pregnancy primes the selective accumulation and activation of maternal regulatory T cells with fetal specificity and extend the role of antigen-experienced regulatory T cells from primary into subsequent pregnancies," Rowe and colleagues conclude.

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