Abstract |
The dominant lymphocytes in human and murine implantation sites are transient, pregnancy-associated uterine natural killer (uNK) cells. These cells are a major source of interferon (IFN)-gamma. Implantation sites in mice lacking uNK cells (alymphoid recombinase activating gene [RAG]-2(-/)- common cytokine receptor chain gamma [gamma(c)](-/)-) or IFN-gamma signaling (IFN-gamma(-/)- or IFN-gammaRalpha(-/)-) fail to initiate normal pregnancy-induced modification of decidual arteries and display hypocellularity or necrosis of decidua. To investigate the functions of uNK cell-derived IFN-gamma during pregnancy, RAG-2(-/)-gamma(c)(-/)- females were engrafted with bone marrow from IFN-gamma(-/)- mice, IFN-gamma signal-disrupted mice (IFN-gammaRalpha(-/)- or signal transducer and activator of transcription [Stat]-1(-/)-), or from mice able to establish normal uNK cells (severe combined immunodeficient [SCID] or C57BL/6). Mated recipients were analyzed at midgestation. All grafts established uNK cells. Grafts from IFN-gamma(-/)- mice did not reverse host vascular or decidual pathology. Grafts from all other donors promoted modification of decidual arteries and decidual cellularity. Grafts from IFN-gammaRalpha(-/)- or Stat-1(-/)- mice overproduced uNK cells, all of which were immature. Grafts from IFN-gamma(-/)-, SCID, or C57BL/6 mice produced normal, mature uNK cells. Administration of murine recombinant IFN-gamma to pregnant RAG-2(-/)-gamma(c)(-/)- mice initiated decidual vessel modification and promoted decidual cellularity in the absence of uNK cells. These in vivo findings strongly suggest that uNK cell-derived IFN-gamma modifies the expression of genes in the uterine vasculature and stroma, which initiates vessel instability and facilitates pregnancy-induced remodeling of decidual arteries.
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Authors | A A Ashkar, J P Di Santo, B A Croy |
Journal | The Journal of experimental medicine
(J Exp Med)
Vol. 192
Issue 2
Pg. 259-70
(Jul 17 2000)
ISSN: 0022-1007 [Print] United States |
PMID | 10899912
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, CD
- DNA-Binding Proteins
- Rag2 protein, mouse
- Receptors, Tumor Necrosis Factor
- Receptors, Tumor Necrosis Factor, Type I
- Tumor Necrosis Factor-alpha
- V(D)J recombination activating protein 2
- Interferon-gamma
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Topics |
- Animals
- Antigens, CD
(physiology)
- DNA-Binding Proteins
(physiology)
- Decidua
(physiology)
- Female
- Interferon-gamma
(physiology)
- Killer Cells, Natural
(physiology)
- Mice
- Mice, Inbred C57BL
- Mice, SCID
- Pregnancy
- Pregnancy, Animal
(physiology)
- Receptors, Tumor Necrosis Factor
(physiology)
- Receptors, Tumor Necrosis Factor, Type I
- Tumor Necrosis Factor-alpha
(physiology)
- Uterus
(blood supply, immunology)
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