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Differential education of human fetal natural killer cells provides a mechanism for fetal-maternal tolerance. (P4458)

Authors :
Martin Ivarsson
Liyen Loh
Nicole Marquardt
Niklas Björkström
Magnus Westgren
Douglas Nixon
Jakob Michaelsson
Source :
The Journal of Immunology. 190:52.46-52.46
Publication Year :
2013
Publisher :
The American Association of Immunologists, 2013.

Abstract

Little is known about the human fetal immune system, but it has for long been considered as immature and unresponsive. Here we have investigated the development and function of human fetal natural killer (NK) cells. Using advanced flow cytometry, the phenotype and function of fetal NK cells was examined. In contrast to the notion that the fetal immune system is immature, we found that human fetal NK cells differentiate as early as gestational week 15 in utero, evidenced by the presence of NK cells with decrease in CD94/NKG2A and increase in CD16 and KIR expression. NK cells with varying degrees of differentiation were found in the fetal lung, liver, spleen, lymph nodes and bone marrow. Moreover, we show that fetal NK cells are highly responsive to cytokine stimulation and are capable of killing target cells both via natural cytotoxicity and by antibody-dependent cellular cytotoxicity. Strikingly, and in contrast to the education of adult NK cells, we demonstrate that while education via CD94/NKG2A was established in fetal NK cells, both self- and non-self KIR expression rendered fetal NK cells hyporesponsive, thus potentially blunting the response to maternal allogeneic cells. Fetal NK cells were also found to be highly sensitive to TGF-β-mediated inhibition as compared to adult NK cells. Taken together, our data indicate a fundamental difference in the education and regulation of fetal compared to adult NK cells, which have implications for fetal-maternal tolerance in utero.

Subjects

Subjects :
Immunology
Immunology and Allergy

Details

ISSN :
15506606 and 00221767
Volume :
190
Database :
OpenAIRE
Journal :
The Journal of Immunology
Accession number :
edsair.doi...........f868b99f73f77c534aa06c9b14dc86e1
Full Text :
https://doi.org/10.4049/jimmunol.190.supp.52.46