Human uterine lymphocytes

King, Ashley; Burrows, Tanya D.; Verma, Sanjay; Hiby, Susan E.; Loke, Y.W.

doi:10.1093/humupd/4.5.480

Cited by 200 publications

(96 citation statements)

References 43 publications

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“…Although hematopoeitic stem cells occur in human uteri (25), in vitro assays show that human CD56 bright blood NK cells, the minor blood NK cell type, gain in functional interactions with endothelium of the decidua basalis at the preovulatory menstrual cycle surge in luteinizing hormone. This gain in potential for NK cell egress into decidua predicts uterine receptivity for transferred embryos (26) and is consistent with the dominance of CD56 bright NK cell subset in decidua (27).…”

supporting

confidence: 72%

Aberrant Endometrial Features of Pregnancy in Diabetic NOD Mice

et al. 2007

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OBJECTIVE-Pregnant diabetic women are at a 4 -12 times higher risk for preeclampsia, an urgent acute-onset complication of mid-to late gestation, than normal pregnant women. Hallmarks of preeclampsia are hypertension, proteinuria, and incomplete modification of endometrial spiral arteries. Transient proangiogenic lymphocytes called uterine natural killer (uNK) cells are implicated in human and rodent spiral artery modification. We studied mid-to late gestations in spontaneously type 1 diabetic NOD mice to investigate whether diabetes alters uNK cell homing and/or function.RESEARCH DESIGN AND METHODS-Normoglycemic, prediabetic, and diabetic NOD mice and controls were mated. Lymphocytes and endometrial endothelium and decidua were studied histologically and in functional assays.RESULTS-Conception accelerated progression to overt diabetes in NOD females who had limited spiral artery development, heavier placentas, and lighter fetuses displaying numerous birth defects compared with controls. UNK cell numbers were reduced in the decidua basalis of diabetic females, whereas interferon-␥ production was elevated. In diabetic NOD mice, decidual expression of the mucosal vascular addressin cell adhesion molecule (MAdCAM)-1 was aberrant in position, whereas vascular cell adhesion molecule (VCAM)-1 expression was reduced. Assays of lymphocyte adhesion to tissue sections under shear forces indicated that diabetes compromises the potential homing functions of both endometrial endothelium and peripheral NK cells.CONCLUSIONS-In diabetes, gestational endometrium has immune and vascular defects that likely contribute to murine fetal loss and birth defects. Analogous problems and preeclampsia in diabetic women may involve similar mechanisms. Diabetes

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confidence: 72%

Aberrant Endometrial Features of Pregnancy in Diabetic NOD Mice

et al. 2007

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“…HLA-G is expressed primarily on trophoblast cells of the fetus that invade maternal decidua during early pregnancy. Signaling through KIR2DL4 might be of particular relevance in that context because NK cells represent Ͼ80% of decidual lymphocytes and contact invading fetal trophoblast cells during pregnancy (32,33). Ponte et al (17) have reported expression of KIR2DL4 (also called p49) on NK cells present at the maternal-fetal interface, but not on peripheral NK cells.…”

Section: Discussionmentioning

confidence: 99%

KIR2DL4 (CD158d), an NK Cell-Activating Receptor with Inhibitory Potential

Faure

Long

2002

The Journal of Immunology

220

170

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KIR2DL4 (CD158d) is an unusual member of the killer cell Ig-like receptor family expressed in all NK cells and some T cells. KIR2DL4 activates the cytotoxicity of NK cells, despite the presence of an immunoreceptor tyrosine-based inhibition motif (ITIM) in its cytoplasmic tail. The role of this ITIM on the activating function of KIR2DL4, and whether it can provide inhibitory signals, is not known. Mutated forms of KIR2DL4 were engineered that lacked either the tyrosine in the ITIM or an arginine-tyrosine motif in the transmembrane region that is required for the activation signal. The activity of the mutated KIR2DL4 molecules was tested in a redirected lysis assay. The ITIM was not necessary for activation of lysis by KIR2DL4. The activation signal of KIR2DL4 was sensitive to inhibition by another ITIM-containing receptor. The activation-deficient mutant of KIR2DL4 inhibited the signal delivered by the activating receptor CD16. In pull-down experiments with GST fusion proteins, the tyrosine-phosphorylated cytoplasmic tail of KIR2DL4 bound the Src homology 2-containing phosphatases 1 and 2, as did the tail of the inhibitory receptor KIR2DL1. Therefore, KIR2DL4 has inhibitory potential in addition to its activating function.

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“…Since the HLA-E/G nonamer complex can evoke an inhibitory or stimulatory response from NK cells (14) and since relative surface levels are likely to directly influence the efficiency of either inhibition or stimulation via CD94-NKG2, it is plausible that there is significant room for modulation of function in the arena of the maternal-placental immune interaction. Indeed, a unique NK response is associated with pregnancy (48), and rather than acting to inhibit NK activity in the maternal decidua, HLA-E may indeed act to stimulate NK to secrete cytokines appropriate for a stable immunological environment. The proper balance of inhibition and stimulation to yield a stable pregnancy may require higher or lower levels of HLA-E, depending upon other immunological and genetic factors present, thus conceivably providing strong selection on a newly introduced HLA-E allele.…”

Section: Discussionmentioning

confidence: 99%

HLA-E Allelic Variants

Strong¹,

Holmes²,

Li³

et al. 2003

Journal of Biological Chemistry

268

114

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Previous studies of HLA-E allelic polymorphism have indicated that balancing selection may be acting to maintain two major alleles in most populations, indicating that a functional difference may exist between the alleles. The alleles differ at only one amino acid position, where an arginine at position 107 in HLA-E*0101 (E R ) is replaced by a glycine in HLA-E*0103 (E G ). To investigate possible functional differences, we have undertaken a study of the physical and biochemical properties of these two proteins. By comparing expression levels, we found that whereas steady-state protein levels were similar, the two alleles did in fact differ with respect to cell surface levels. To help explain this difference, we undertook studies of the relative differences in peptide affinity, complex stability, and three-dimensional structure between the alleles. The crystal structures for HLA-E G complexed with two distinct peptides were determined, and both were compared with the HLA-E R structure. No significant differences in the structure of HLA-E were induced as a result of binding different peptides or by the allelic substitution at position 107. However, there were clear differences in the relative affinity for peptide of each heavy chain, which correlated with and may be explained by differences between their thermal stabilities. These differences were completely consistent with the relative levels of the HLA-E alleles on the cell surface and may indeed correlate with functional differences. This in turn may help explain the apparent balancing selection acting on this locus.

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Human uterine lymphocytes

Cited by 200 publications

References 43 publications

Aberrant Endometrial Features of Pregnancy in Diabetic NOD Mice

Aberrant Endometrial Features of Pregnancy in Diabetic NOD Mice

KIR2DL4 (CD158d), an NK Cell-Activating Receptor with Inhibitory Potential

HLA-E Allelic Variants

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