Document Detail


Gestation stage-dependent mechanisms of invariant natural killer T cell-mediated pregnancy loss.
MedLine Citation:
PMID:  16537414     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Stimulation of CD1d-restricted semiinvariant natural killer T cells by using the CD1d ligand alpha-galactosylceramide (alphaGalCer) induces pregnancy loss in mice through an ill-defined mechanism involving TNF, IFN-gamma, and perforin. In this article, we demonstrate that during early gestation, alphaGalCer efficiently induced pregnancy loss in C57BL/6J and BALB/cJ mice in a perforin-dependent manner. In contrast, during midgestation perforin was no longer required for pregnancy loss. Concomitant with the loss of a perforin requirement at midgestation was the emergence of strain-dependent variations in susceptibility to alphaGalCer-induced pregnancy loss. Whereas pregnant C57BL/6J mice remained susceptible to alphaGalCer at midgestation, pregnant BALB/cJ mice were resistant to its effects. Pregnancy loss during midgestation was correlated with dramatically higher serum cytokine levels, including TNF and IL-2, in the susceptible C57BL/6J strain compared with the resistant BALB/cJ strain. Thus, the stage of gestation defined two distinct mechanisms of pregnancy loss: a perforin-dependent mechanism operating at early gestation and a perforin-independent, cytokine-dominated mechanism operating after midgestation.
Authors:
Jonathan E Boyson; Nisha Nagarkatti; Leena Nizam; Mark A Exley; Jack L Strominger
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-03-14
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  103     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-03-22     Completed Date:  2006-05-11     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4580-5     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD1 / analysis*
Antigens, CD1d
Female
Galactosylceramides / pharmacology
Interleukin-2 / blood
Killer Cells, Natural / drug effects,  immunology*
Ligands
Membrane Glycoproteins / metabolism
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Perforin
Pore Forming Cytotoxic Proteins
Pregnancy
Premature Birth / genetics,  immunology*,  pathology
T-Lymphocytes / drug effects,  immunology*
Tumor Necrosis Factor-alpha / analysis
Grant Support
ID/Acronym/Agency:
AI 053330/AI/NIAID NIH HHS; F32 HD008515/HD/NICHD NIH HHS; P20 RR021905/RR/NCRR NIH HHS; R01 AI067897/AI/NIAID NIH HHS; R01 AI067897-01A2/AI/NIAID NIH HHS; R01 AI067897-02/AI/NIAID NIH HHS; R01 AI067897-03/AI/NIAID NIH HHS; R01 AI067897-04/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD1; 0/Antigens, CD1d; 0/Galactosylceramides; 0/Interleukin-2; 0/Ligands; 0/Membrane Glycoproteins; 0/Pore Forming Cytotoxic Proteins; 0/Tumor Necrosis Factor-alpha; 0/alpha-galactosylceramide; 126465-35-8/Perforin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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