PD-1 regulates T cell proliferation in a tissue and subset-specific manner during normal mouse pregnancy

Immunol Invest. 2013;42(5):385-408. doi: 10.3109/08820139.2013.782317. Epub 2013 Jun 19.

Abstract

The regulation of T cell homeostasis during pregnancy has important implications for maternal tolerance and immunity. Evidence suggests that Programmed Death-1 (PD-1) participates in regulation of T cell homeostasis and peripheral tolerance. To examine the contribution of PD-1 signaling on T cell homeostasis during normal mouse pregnancy, we examined T cell number or proportion, PD-1 expression, proliferation, and apoptosis by flow cytometry, BrdU incorporation, and TUNEL assay in pregnant mice given anti-PD-1 blocking antibody or control on days 10, 12, and 14 of gestation. We observed tissue, treatment, and T cell-specific differences in PD-1 expression. Both pregnancy and PD-1 blockade increased T cell proliferation in the spleen, yet this effect was limited to CD4 T cells in the uterine- draining nodes. In the uterus, PD-1 blockade markedly altered the composition of the T cell pool. These studies support the idea that pregnancy is a state of dynamic T cell homeostasis and suggest that this state is partially supported by PD-1 signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Blocking / administration & dosage
  • Antigens, Differentiation / immunology*
  • Apoptosis / drug effects
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Female
  • Homeostasis / drug effects
  • Homeostasis / immunology
  • Lymphocyte Count
  • Mice
  • Mice, Inbred C57BL
  • Organ Specificity
  • Peripheral Tolerance / drug effects
  • Pregnancy / immunology*
  • Programmed Cell Death 1 Receptor
  • Spleen / immunology*
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • Uterus / immunology*

Substances

  • Antibodies, Blocking
  • Antigens, Differentiation
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor