GM-CSF is an essential regulator of T cell activation competence in uterine dendritic cells during early pregnancy in mice
In: Journal of immunology (Baltimore, Md. : 1950), Jg. 185 (2010-10-27), Heft 11
Online
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Zugriff:
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.
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GM-CSF is an essential regulator of T cell activation competence in uterine dendritic cells during early pregnancy in mice
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Autor/in / Beteiligte Person: | Robertson, Sarah A. ; Moldenhauer, Lachlan M. ; Hayball, John D. ; Sarah N. Hudson Keenihan ; Moldenhauer, Lachlan M ; Keenihan, Sarah N ; Hayball, John D ; Robertson, Sarah A |
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Zeitschrift: | Journal of immunology (Baltimore, Md. : 1950), Jg. 185 (2010-10-27), Heft 11 |
Veröffentlichung: | 2010 |
Medientyp: | unknown |
ISSN: | 1550-6606 (print) |
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