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Type: Journal article
Title: GM-CSF is an essential regulator of T cell activation competence in uterine dendritic cells during early pregnancy in mice
Author: Moldenhauer, L.
Keenihan, S.
Hayball, J.
Robertson, S.
Citation: Journal of Immunology, 2010; 185(11):7085-7096
Publisher: Amer Assoc Immunologists
Issue Date: 2010
ISSN: 0022-1767
Statement of
Lachlan M. Moldenhauer, Sarah N. Keenihan, John D. Hayball, and Sarah A. Robertson
Abstract: Uterine dendritic cells (DCs) are critical for activating the T cell response mediating maternal immune tolerance of the semiallogeneicfetus. GM-CSF (CSF2), a known regulator of DCs, is synthesized by uterine epithelial cells during induction of tolerance in early pregnancy. To investigate the role of GM-CSF in regulating uterine DCs and macrophages, Csf2-null mutant and wild-type mice were evaluated at estrus, and in the periconceptual and peri-implantation periods. Immunohistochemistry showed no effect of GM-CSF deficiency on numbers of uterine CD11c+ cells and F4/80+ macrophages at estrus or on days 0.5 and 3.5 postcoitum, but MHC class II+ and class A scavenger receptor+ cells were fewer. Flow cytometry revealed reduced CD80 and CD86 expression by uterine CD11c+ cells and reduced MHC class II in both CD11c+ and F4/80+ cells from GM-CSF–deficient mice. CD80 and CD86 were induced in Csf2−/− uterine CD11c+ cells by culture with GM-CSF. Substantially reduced ability to activate both CD4+ and CD8+ T cells in vivo was evident after delivery of OVA Ag by mating with Act-mOVA males or transcervical administration of OVA peptides. This study shows that GM-CSF regulates the efficiency with which uterine DCs and macrophages activate T cells, and it is essential for optimal MHC class II- and class I-mediated indirect presentation of reproductive Ags. Insufficient GM-CSF may impair generation of T cell-mediated immune tolerance at the outset of pregnancy and may contribute to the altered DC profile and dysregulated T cell tolerance evident in infertility, miscarriage, and preeclampsia.
Keywords: Uterus
Antigen-Presenting Cells
Dendritic Cells
T-Lymphocyte Subsets
Mice, Inbred C57BL
Mice, Transgenic
Mice, Knockout
Granulocyte-Macrophage Colony-Stimulating Factor
Pregnancy Proteins
Histocompatibility Antigens Class I
Histocompatibility Antigens Class II
Epitopes, T-Lymphocyte
Lymphocyte Activation
Organ Specificity
Amino Acid Sequence
Molecular Sequence Data
Rights: Copyright © 2010 by The American Association of Immunologists, Inc.
DOI: 10.4049/jimmunol.1001374
Appears in Collections:Aurora harvest
Obstetrics and Gynaecology publications

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