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J Reprod Immunol. 2009 Jun;80(1-2):12-21. doi: 10.1016/j.jri.2008.12.001. Epub 2009 Apr 14.

Maternal PD-1 regulates accumulation of fetal antigen-specific CD8+ T cells in pregnancy.

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1
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160-7400, USA.

Abstract

The failure to reject the semi-allogeneic fetus suggests that maternal T lymphocytes are regulated by potent mechanisms in pregnancy. The T cell immunoinhibitory receptor, Programmed Death-1 (PD-1), and its ligand, B7-H1, maintain peripheral tolerance by inhibiting activation of self-reactive lymphocytes. Here, we investigated the role of the PD-1/B7-H1 pathway in maternal tolerance of the fetus. Antigen-specific maternal T cells both proliferate and upregulate PD-1 in vivo at mid-gestation in response to paternally inherited fetal antigen. In addition, when these cells carry a null deletion of PD-1, they accumulate excessively in the uterus-draining lymph nodes (P<0.001) without a concomitant increase in proliferation. In vitro assays showed that apoptosis of antigen-specific CD8(+) PD-1(-/-) cells was reduced following peptide stimulation, suggesting that the accumulation of these cells in maternal lymph nodes is due to decreased cell death. However, the absence of neither maternal PD-1 nor B7-H1 had detectable effects on gestation length, litter size, or pup weight at birth in either syngeneic or allogeneic pregnancies. These results suggest that PD-1 plays a previously unrecognized role in maternal-fetal tolerance by inducing apoptosis of paternal antigen-specific T cells during pregnancy, thereby controlling their abundance.

PMID:
19368976
PMCID:
PMC2764286
DOI:
10.1016/j.jri.2008.12.001
[Indexed for MEDLINE]
Free PMC Article

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