Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 112, Issue 43, Pages 13312-13317Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1517724112
Keywords
pregnancy; decidua; human; HCMV; cytotoxicity
Categories
Funding
- National Institutes of Health [AI053330]
- March of Dimes Grant [6-FY14-453]
- Portuguese Foundation for Science and Technology (FCT) [SFRH/BD/33885/2009]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/33885/2009] Funding Source: FCT
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The interaction of noncytotoxic decidual natural killer cells (dNK) and extravillous trophoblasts (EVT) at the maternal-fetal interface was studied. Confocal microscopy revealed that many dNK interact with a single large EVT. Filamentous projections from EVT enriched in HLA-G were shown to contact dNK, and may represent the initial stage of synapse formation. As isolated, 2.5% of dNK contained surface HLA-G. However, surface HLA-G-negative dNK contained internalized HLA-G. Activation of dNK resulted in the disappearance of internalized HLA-G in parallel with restoration of cytotoxicity. Surface HLA-G was reacquired by incubation with EVT. This HLA-G cycle of trogocytosis, endocytosis, degradation, and finally reacquisition provides a transient and localized acquisition of new functional properties by dNK upon interaction with EVT. Interruption of the cycle by activation of dNK by cytokines and/or viral products serves to ensure the NK control of virus infection at the interface, and is illustrated here by the response of dNK to human cytomegalo virus (HCMV)-infected decidual stromal cells. Thus, the HLA-G cycle in dNK can provide both for NK tolerance and antiviral immunity.
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