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https://hdl.handle.net/2440/62640
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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 1550-6606 |
Statement of Responsibility: | 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 Endometrium Antigen-Presenting Cells Dendritic Cells T-Lymphocyte Subsets Animals Mice, Inbred C57BL Mice, Transgenic Mice, Knockout Mice 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 Pregnancy Molecular Sequence Data Female Male |
Rights: | Copyright © 2010 by The American Association of Immunologists, Inc. |
DOI: | 10.4049/jimmunol.1001374 |
Published version: | http://dx.doi.org/10.4049/jimmunol.1001374 |
Appears in Collections: | Aurora harvest Obstetrics and Gynaecology publications |
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