Phenotypic heterogeneity and recycling capacity of natural killer cells in normal human pregnancy

doi:10.1016/0165-0378(87)90017-9

Journal of Reproductive Immunology

Volume 11, Issue 2, June 1987, Pages 135-145

https://doi.org/10.1016/0165-0378(87)90017-9 Get rights and content

Abstract

Natural killer (NK) cells have the ability to kill a variety of target cell types and the possibility that such cells could mount an effective attack on the developing fetus has not been discounted. The present study extends previous work showing that maternal NK reactivity against K562 target cells (TC) is reduced during pregnancy. Here we demonstrate using cytotoxicity assays at both the population and single cell level that, although depressed in number, maternal NK cells exhibiting the capacity to kill K562 TC are as lytically active in their ability to recycle and destroy multiple TC as NK cells from non-pregnant females. Moreover, two colour immunofluorescence analysis of the NK cell-associated markers Leu-7 and Leu-11b indicates that, in addition to a reduction in the absolute number of TC conjugate-forming cells, pregnant females present in their peripheral blood a larger proportion of TC-binding Leu-7⁺11⁻ cells. These cells may be lytically immature. Small changes in NK cell profile and activity in maternal peripheral blood may be indicative of much more significant changes at the feto-maternal interface. It is, however, clear that pregnant females retain a population of highly active NK cells, thus minimising the possibility of immunocompromise.

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J. Clin. Lab. Immunol.

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Cited by (20)

Functional prominence of natural killer cells and natural killer T cells in pregnancy and infertility: A comprehensive review and update
2022, Pathology Research and Practice
Citation Excerpt :
They concluded that miR-30e is involved in creating an immune tolerance periphery in the maternal-fetal interface [32]. In a normal human gestation, the lytic activity of NK cells and the number of CD16− NK cells in the peripheral blood are reduced compared to non-pregnant individuals [56,57]. It has also been observed that, in these cells, the expression of the inhibitory KIR receptor (CD94/NKG2A) increases in the primary weeks of pregnancy and reaches a maximum by the third month, and then decreases to baseline [58].
During pregnancy, complicated connections are formed between a mother and a fetus. In a successful pregnancy, the maternal-fetal interface is affected by dynamic changes, and the fetus is protected against the mother’s immune system. Natural killer (NK) cells are one of the immune system cells in the female reproductive system that play an essential role in the physiology of pregnancy. NK cells not only exist in peripheral blood (PB) but also can exist in the decidua. Studies have suggested multiple roles for these cells, including decidualization, control of trophoblast growth and invasion, embryo acceptance and maintenance by the mother, and facilitation of placental development during pregnancy. Natural killer T (NKT) cells are another group of NK cells that play a crucial role in the maintenance of pregnancy and regulation of the immune system during pregnancy. Studies show that NK and NKT cells are not only effective in maintaining pregnancy but also can be involved in infertility-related diseases. This review focuses on NK and NKT cells biology and provides a detailed description of the functions of these cells in implantation, placentation, and immune tolerance during pregnancy and their role in pregnancy complications.
Recent insights into the impact of immune dysfunction on reproduction in autoimmune thyroiditis
2021, Clinical Immunology
Citation Excerpt :
The other 10% are CD56brightCD16−NK cells, which have immunoregulatory functions [84]. During normal pregnancy, which is regulated by hormones, the number and dissolution activity of CD56dimCD16+NK cells decrease [85,86], while the expression of inhibitory receptors increases [87]. NK cells dysregulation in the peripheral blood is closely related to reproductive failures, including RM and infertility [88].
Autoimmune thyroiditis (AIT) is a common organ-specific autoimmune disease with a high incidence among women of childbearing age. Recent studies have reported that women with AIT are more susceptible to infertility, miscarriage and preterm birth. It has been investigated that abnormal changes in maternal immune system and maternal–fetal interface can dampen the immune tolerance between mother and fetus, which underlie the pathogenesis of adverse pregnancy outcomes. Hence, we summarize the immunological changes related to adverse reproductive outcomes in AIT and highlight the respective contributions of both humoral and cellular immune dysfunctions to pregnancy failures. Moreover, the direct impacts of AIT on maternal–fetal immune activation and biological influences to trophoblasts are discussed as well. All these associations require confirmation in larger studies, and the pathogenic mechanisms need to be better understood, which might provide useful information for clinical diagnosis and therapy of AIT.
Pregnancy as a model for aging
2020, Ageing Research Reviews
Citation Excerpt :
During uncomplicated pregnancy, NK phenotype and quantity fluctuate greatly. Peripheral blood NK quantity decreases due to a reduction in the CD16+ (Gregory et al., 1985; Beer et al., 1996), and the cells exhibit decreased lytic activity (Gregory et al., 1987). There is also a fluctuation of inhibitory receptors among peripheral T cells and NK cells in early pregnancy, peaking in the third month and declining postpartum (Ponte et al., 1999).
The process of aging can be defined as the sum accumulation of damages and changes in metabolism during the life of an organism, due to both genetic predisposition and stochastic damage. During the gestational period and following parturition, similar damage can be seen due to the strenuous effect on the maternal body, exhibited on both the physiological and cellular level. In this review, we will focus on the similar physiological and cellular characteristics exhibited during pregnancy and aging, including induction of and response to oxidative stress, inflammation, and degradation of telomeres. We will evaluate any similar processes between aging and pregnancy by comparing common biomarkers, pathologies, and genetic and epigenetic effects, to establish the pregnant body as a model for aging. This review will approach the connection both in respect to current theories on aging as a byproduct of natural selection, and regarding unrelated biochemical similarities between the two, drawing on existing studies and models in humans and other species where relevant alike. Furthermore, we will show the response of the pregnant body to these changes, and through that illuminate unique areas of potential study to advance our knowledge of the maladies relating to aging and pregnancy, and an avenue for solutions.
Immunology of pregnancy: towards a unifying hypothesis
1992, European Journal of Obstetrics and Gynecology and Reproductive Biology
The variable findings of hormonal-immunoregulation and the variable cellular and humoral immune responses in pregnancy have been considered in relationship to the physiological response. From such considerations it appears that the peripheral blood lymphocyte/leukocyte response in pregnancy is not important, but rather the local uterine immune response at implantation and throughout pregnancy. It is proposed, and evidence is presented, that a normal allogeneic immune response is initiated at the time of implantation of the blastocyst. This immune response regulates the invasive nature of the trophoblast and initiates the first stage of parturition. The initiation and maintenance of this immune response is based on an interplay between maternal and paternal HLA and trophoblast antigens. In the case of HLA-incompatible donor-recipient blastocyst transplants, a more pivotal role for immunoregulation by trophoblast antigens is proposed. This is because it is considered that the local uterine immune response suppresses the expression of allogeneic HLA. This concept is further developed in terms of haploid HLA suppression on maternal and fetal lymphocytes that cross the placenta. This is considered to allow the interaction of these lymphocytes with each other and explains maternal transfer of cell-mediated immunity.
Natural killer cell activity from pregnant subjects is modulated by RU 486
1992, American Journal of Obstetrics and Gynecology
Natural killer cells form an integral component of the body's innate immune system. Natural killer cell activity is reduced during pregnancy, especially in the latter half. To investigate the role progesterone may play in immunomodulating natural killer cell activity during pregnancy, we evaluated the effect of RU 486 on natural killer cells isolated from pregnant subjects. Natural killer cell activity was measured with an 18-hour, Chromium 51 release, microcytotoxicity assay with K-562 cells as target cells. We demonstrated that RU 486, in a concentration range from 5 to 40 \mumol/L, augmented natural killer activity threefold to fivefold over baseline. This augmentation of activity was suppressed to baseline by the addition of excess progesterone. The addition of hydrocortisone resulted in an insignificant reduction in this augmented activity. This study suggests that progesterone may play a role as an immunomodulating factor in maternal acceptance of the fetal allograft.
Origins and maturation patterns of azurocytes in the meadow vole (Microtus pennsylvanicus)
1991, Comparative Biochemistry and Physiology. Part C, Comparative
1. The origins, maturation sequence, and traffic patterns of azurocytes (AZ) were studied in vivo in the meadow vole (Microtus pennsylvanicus) with the aid of various biological response modifiers.
2. AZ originated from lymphocyte-like precursors in the bone marrow. These precursors entered into intense mitotic activity in the bone marrow following progestin treatment.
3. While still in the bone marrow, AZ precursors differentiated into granulated cells with some of the histochemical properties of AZ.
4. At this time, maturation could be blocked completely with cyclophosphamide. Hydroxyurea and cyclosporin A inhibited maturation significantly, but did not block it.
5. Estradiol, hydrocortisone, prostaglandin E₂, and conditioned medium had no effect on the numbers of cells induced.
6. Transitional stages between a granulated bone marrow precursor and an AZ were rarely observed, suggesting rapid synthesis of AZ inclusions upon terminal differentiation.
7. After release from the bone marrow, AZ were common in the blood only. Modest numbers of cells were also found in the red pulp of the spleen, and the thymic cortex.
8. AZ in the thymus were sometimes found in clusters, and were often associated with septa. Very low numbers of mature AZ were detected in the bone marrow.
9. AZ were absent from lymph nodes and Peyers patches, and were never observed in the B-lymphocyte areas of the spleen.
10. Based on experiments with dextran sulphate, AZ and their precursors never entered the recirculating lymphocyte population. AZ in the blood or tissues were never observed in mitosis, and were never observed degranulating.
11. Cyclophosphamide or hydrocortisone had no effect on AZ numbers when administered at the peak of their occurrence in the blood.
12. Although no clear function of the AZ was elucidated, experiments confirmed a high degree of similarity between its properties and those of cytotoxic cells found in other mammals.

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Journal of Reproductive Immunology

Abstract

References (24)

Spontaneous human lymphocyte-mediated cytotoxicity against tumour target cells

Immunologic regulation of fetal-maternal balance

Adv. Immunol.

Effects of diethylstilbestrol on human natural killer cells in vitro

Immunopharmacology

Natural killer activity during pregnancy

Am. J. Obstet. Gynecol.

A monoclonal antibody reactive against purified human natural killer cells and granulocytes

Immunol. Lett.

A differentiation antigen of human NK and K cells identified by a monoclonal antibody (HNK-1)

J. Immunol.

Characterization of human granular lymphocyte subpopulations expressing HNK-1 (Leu-7) and Leu-11 antigens in the blood and lymphoid tissues from fetuses, neonates and adults

Eur. J. Immunol.

Maternal natural killer cell activity during normal pregnancy and pre-eclampsia

Am. J. Reprod. Immunol.

K562-a human erythroleukaemic cell line

Int. J. Cancer

Suppression of natural cell-mediated cytotoxicity in man by maternal and neonatal serum

Clin. Exp. Immunol.

Immunobiology of the maternal-fetal relationship

Cytotoxic reactivity of human natural killer (NK) cells during normal pregnancy: a longitudinal study

J. Clin. Lab. Immunol.

Cited by (20)

Functional prominence of natural killer cells and natural killer T cells in pregnancy and infertility: A comprehensive review and update

Recent insights into the impact of immune dysfunction on reproduction in autoimmune thyroiditis

Pregnancy as a model for aging

Immunology of pregnancy: towards a unifying hypothesis

Natural killer cell activity from pregnant subjects is modulated by RU 486

Origins and maturation patterns of azurocytes in the meadow vole (Microtus pennsylvanicus)