2. Academic Validation
  3. The HLA-G cycle provides for both NK tolerance and immunity at the maternal-fetal interface

The HLA-G cycle provides for both NK tolerance and immunity at the maternal-fetal interface

  • Proc Natl Acad Sci U S A. 2015 Oct 27;112(43):13312-7. doi: 10.1073/pnas.1517724112.
Tamara Tilburgs 1,  J Henry Evans 2,  Ângela C Crespo 3,  Jack L Strominger 1
Affiliations

Affiliations

  • 1 Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138; tilburgs@fas.harvard.edu jlstrom@fas.harvard.edu.
  • 2 Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138;
  • 3 Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138; Doctoral Programme in Experimental Biology and Biomedicine, Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal.
PMID: 26460007 DOI: 10.1073/pnas.1517724112
Abstract

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.

Keywords

HCMV; cytotoxicity; decidua; human; pregnancy.

Figures