title: PD-1 regulates T cell proliferation in a tissue and subset-specific manner during normal mouse pregnancy.
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.
authors.affiliation: University of Vermont College of Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, Burlington, VT 05405, USA.
authors.forename: Michelle T
authors.initials: MT
authors.lastname: Shepard
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Bonney
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D000943:Antigens, Differentiation / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006706:Homeostasis / Q000187:drug effects / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D061166:Peripheral Tolerance / Q000187:drug effects; D011247:Pregnancy / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor; D013154:Spleen / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D014599:Uterus / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; D000943:Antigens, Differentiation; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor