NK cells and trophoblasts: partners in pregnancy - PubMed (original) (raw)

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NK cells and trophoblasts: partners in pregnancy

Peter Parham. J Exp Med. 2004.

Abstract

In placental mammals, viviparity--the production of living young within the mother's body--evolved under the auspices of the immune system. Elements of immunity were incorporated, giving pregnancy a mildly inflammatory character. Formation of the placenta, the organ that feeds the fetus, involves a cooperation between maternal natural killer (NK) cells and fetal trophoblast cells that remodels the blood supply. Recent research reveals that this process and human reproductive success are influenced by polymorphic HLA-C ligands and their killer cell immunoglobulin-like receptors (KIR).

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Figures

Figure 1.

Figure 1.

In pregnancy, the spiral arteries are remodeled by extravillous trophoblast cells and NK cells. The left panel shows the nonpregnant endometrium in the secretory phase of the menstrual cycle just before menstruation. The right panel shows the endometrium in the second half of normal pregnancy when the spiral arteries are remodeled to a depth that penetrates the myometrium. The middle panel shows the situation in preeclampsia where the extent and depth of remodeling is less than in normal pregnancy. These vascular changes are effected by extravillous trophoblast cells (EVT) with the help of activated NK cells. In the process, the enlarged vessels become lined with endovascular trophoblast cells (ENVT) (10).

Figure 2.

Figure 2.

Preeclampsia is associated with uterine NK cells of KIR genotype AA and the presence of HLA-C2 on the surface of extravillous trophoblast cells. An extravillous trophoblast (EVT) is shown interacting with a maternal uterine NK cell. EVT are the only trophoblast cells that express MHC class I. The HLA-C2 molecule is shown interacting with its cognate inhibitory receptor KIR2DL1. The inhibition due to this ligand–receptor interaction favors preeclampsia in the absence of compensating activating KIR. The functional KIR genes of a group A haplotype are shown in order below the NK cell. The KIR nomenclature give the number of a receptor's extracellular domains (2D or 3D) the length of the cytoplasmic tail (long or short) and a final number distinguishing receptors with similar structure. Long-tailed KIR inhibit and short-tailed KIR activate, except KIR2DL4 which does both. HLA-C2 refers to any one of the HLA-C allotypes that has lysine at position 80. Many other ligand–receptor pairs that contribute to the cell–cell interaction are not depicted.

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