Natural Killer Cells and Dendritic Cells at the Human Feto-maternal Interface: an Effective Cooperation?☆
Introduction
The fetus, which expresses maternal and paternal antigens on its surface, can be perceived as a successful allograft. In humans, invasion of the semiallogeneic trophoblast cells into the decidualized endometrium and the inner third of the myometrium is of vital importance for both the anchoring of the placenta and their connection with the maternal vascular system [1]. During invasion, trophoblast cells encounter a variety of maternal immune-competent cells. The most prominent of these are CD56++ natural killer (NK) cells which can act as cytotoxic effector cells and produce various cytokines [2]. Recent reports have demonstrated the presence of CD83+ mature DCs, DC-SIGN+ (dendritic cell specific ICAM-3 grabbing non-integrin, CD209) immature dendritic cells (iDCs) and DEC205+ intermediate DCs in human decidua [3], [4], [5]. Besides their well-known role as potent antigen presenting cells (APCs), DCs can also induce peripheral tolerance [6]. DCs are therefore suitable candidates to fulfil the difficult task of providing both tolerance towards the invading allograft and initiating a maternal defensive immune response to foreign antigens when necessary.
Section snippets
Uterine NK cells
The uterine mucosa of early pregnancy, the decidua, is remarkable for its dominant population of CD45+ leukocytes. Within that population, uterine natural killer (uNK) cells are the main subpopulation and have been the subject of several recent reviews [2], [7]. They exhibit a round shape and contain large granules in the cytoplasm consisting of enzymes such as perforins and granzymes [8]. Uterine NK cells have a unique phenotype (CD3−, CD16−, CD56++) and a markedly different gene expression
Characteristics and functions of dendritic cells
Dendritic cells (DCs) are a heterogeneous population of cells present in the epidermal layer of the skin, in mucosal membranes, in interstitial spaces of solid organs and in lymphoid tissues where they are considered to act as sentinels of the immune system [28]. After an invasion of pathogens has occurred, DC precursors are attracted to these sites of inflammation by chemokines such as MIP-1 α/β [29]. The expression of chemokine receptors such as chemokine-receptor 1 (CCR1) and
NK cell/DC cell cross-talk
As uNK cells and DC-SIGN+ iDCs are the dominant populations of leukocytes in human first trimester decidua, the question arises as to whether an interplay between these two cell types could contribute to the symbiosis between the mother and the semiallogeneic fetus.
To date, several in vitro studies have provided evidence for an interaction between peripheral blood NK cells and DCs [62], [63]. The ratio between these cells seems to be of particular significance for the way they influence each
Conclusions
Taking the above-mentioned possible interactions of uNK cells and uterine dendritic cells into account, several challenging questions remain: first, which receptor–ligand interactions are preconditions for an efficient cross-talk between both cell types? Second, does the fetus manipulate the interaction between decidual DCs and uNK cells e.g. by the expression of MHC class I molecules such as HLA-G and -E with the aim that a tolerizing and symbiotic system can develop? By investigating the
Acknowledgements
The authors thank Thomas Hünig, PhD and Kirsty McPherson, PhD, Institute of Immunology and Virology, University of Würzburg, for valuable discussions.
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Supported by grants Di-390/3-1,2 (to J. D.) and KFO124/1-1,2 (to U.K.) from the Deutsche Forschungsgemeinschaft, Bonn.