Infiltrating decidual natural killer cells are associated with spontaneous abortion in mice

Gendron, Roxanne; Baines, Malcolm G.

doi:10.1016/0008-8749(88)90025-1

Cited by 173 publications

(71 citation statements)

References 12 publications

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“…Early work suggested that cellmediated immune mechanisms were responsible for fetal loss as such cell types were evident at abortion sites in murine uteri after xenogeneic transplantation [Croy et al 1982]. Moreover, examination of the resorption sites of an allogeneic, abortion-prone mouse model (CBA/J female Â DBA/2J male) revealed excessive infiltration of uNK cells at implantation sites just before and after spontaneous abortion [Gendron and Baines 1988]. Depletion of NK cells (by injections of anti-asialo GM1 antibody) in this same mouse model resulted in a reduction of the number of resorption sites, while enhancement of NK activity (via poly I:C injections) increased the resorption rate [de Fougerolles and Baines 1987].…”

Section: Uterine Natural Killer Cellsmentioning

confidence: 99%

Embryonic Resorption and Polycyclic Aromatic Hydrocarbons: Putative Immune-mediated Mechanisms

Detmar

Jurisicova

2010

Systems Biology in Reproductive Medicine

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Polycyclic aromatic hydrocarbons (PAHs) are released into the environment as a result of incomplete fossil fuel combustion from industrial furnaces, woodburning stoves, and automobile exhaust fumes; however, the primary source of human exposure to these compounds is cigarette smoke. Embryonic and fetal loss after treatment with high doses of PAHs have been well documented in animal studies; however, few studies have addressed the reproductive consequences of long-term, low-level exposure to these chemicals. We previously reported that low doses of PAHs administered to ICR mice over a period of 9 weeks prior to conception resulted in early embryonic resorptions, whereby treated dams lost approximately 50% of their litter. During the course of these studies, we observed greater numbers of infiltrating uterine natural killer (uNK) cells into the placenta of PAH-exposed conceptuses. While exposure to high levels of PAHs has been shown to be immunosuppressive, increasing evidence suggests that chronic, low-dose exposure to PAHs may stimulate immune cells. Thus, we hypothesized that low-dose, chronic PAH exposure in our mouse model is mediating embryonic resorption by hyperstimulating maternal immune cells. In this review of the literature, we outline the rationale of our argument and present preliminary data, focussing upon PAH-mediated alterations in uNK cell dynamics and how these changes may be linked to early embryonic resorptions.

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Section: Uterine Natural Killer Cellsmentioning

confidence: 99%

Embryonic Resorption and Polycyclic Aromatic Hydrocarbons: Putative Immune-mediated Mechanisms

Detmar

Jurisicova

2010

Systems Biology in Reproductive Medicine

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“…Progesterone is highly expressed during pregnancy, and many studies have demonstrated suppression of NK cell cytotoxic activity during this period (8,44,145,146). Indeed, this progesteronedependent immunomodulation of NK cell activity is thought to be one of the mechanisms that enables pregnancy to proceed to term, as spontaneous pregnancy termination is associated with increased systemic NK activity (32,142) and failure of the fetoplacental unit to suppress uterine NK cell activity (49,50). Interestingly, a recent study of uterine NK cells during pregnancy showed that these cells express both TNF-␣ and inducible nitric oxide synthase (iNOS) in vivo, and this is maintained in the presence of progesterone (61), suggesting that in addition to influencing cytotoxic ability, pregnancy-associated hormones regulate proinflammatory molecule expression by NK cells.…”

Section: Natural Killer Cellsmentioning

confidence: 99%

Sex-Associated Hormones and Immunity to Protozoan Parasites

2001

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Numerous epidemiological and clinical studies have noted differences in the incidence and severity of parasitic diseases between males and females. Although in some instances this may be due to gender-associated differences in behavior, there is overwhelming evidence that sex-associated hormones can also modulate immune responses and consequently directly influence the outcome of parasitic infection. Animal models of disease can often recreate the gender-dependent differences observed in humans, and the role of sex-associated hormones can be confirmed by experimentally altering their levels. Under normal circumstances, levels of sex hormones not only differ between males and females but vary according to age. Furthermore, not only are females of reproductive age subject to the regular hormonal cycles which control ovulation, they are also exposed to dramatically altered levels during pregnancy. It is thus not surprising that the severity of many diseases, including those caused by parasites, has been shown to be affected by one or more of these circumstances. In addition, infection with many pathogens has been shown to have an adverse influence on pregnancy. In this article we review the impact of sex-associated hormones on the immune system and the development and maintenance of immunity to the intracellular protozoan parasites Toxoplasma gondii, Plasmodium spp., and Leishmania spp

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“…(Croy & Kassouf, 1989). It is tempting to speculate that they could themselves be regulated by lymphokines, and secrete some lymphokines, and thus be involved in the control of placental growth (Wegmann et ai, 1989. Furthermore, it has been shown that spontaneous abortion rates in the abortion-prone CBA DBA/2 mouse system correlate with the local infiltration of asialo GM 1-positive cells (Gendron & Baines, 1988). Indeed, it has been shown that embryos are first infiltrated by cells with NK-like activity, and only thereafter by some cytotoxic lymphocytes (Chaouat, 1986).…”

Section: Introductionmentioning

confidence: 99%

“…In this system, there is suggestive evidence that abortion is mediated by asialo GM 1-positive natural effector cells (Chaouat et ai, 1987; Baines & de Fougerolles, 1988). If CBA/J females are immunized against BALB/c lymphocytes before mating, the high résorption rates in CBA/J mice mated with DBA/2 males are prevented (Chaouat et ai, 1983(Chaouat et ai, , 1987(Chaouat et ai, , 1988a and there is no longer accumulation of asialo Gml + cells in the uterus (Gendron & Baines, 1988). Protection against abortion can be adoptively transferred by CBA/J anti-BALB/c immune cells, or cells from the spleens of CBA/J mice that were multiparous by repeated mating to BALB/c males (Chaouat et ai, 1985).…”

Section: Introductionmentioning

confidence: 99%

Control of fetal survival in CBA x DBA/2 mice by lymphokine therapy

Chaouat¹,

Menu²,

Clark³

et al. 1990

Reproduction

470

219

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Summary. In this study, we examined the effect of injecting various cytokines. We report here that tumour necrosis factor (TNF)\g=a\,\g=g\-interferon and interleukin 2 (IL-2) can, in some circumstances, increase fetal resorption rates in abortionprone (CBA/J \m=x\DBA/2) and non-abortion prone (CBA/J \m=x\BALB/c,C3H \m=x\DBA/2) matings: 1000 units TNF enhanced resorptions from 43 to 79% in CBA \m=x\DBA/2, from 7 to 89% in CBA \m=x\ BALB/c, from 5 to 47% in C3H \m=x\ DBA/2. The effect was both gestational age-and dose-dependent. Gamma interferon and R-IL-2 enhanced resorptions from 38 to 68% and 76% respectively in the CBA/J \m=x\ DBA/2 mating combination, whereas the rates in CBA/J \m=x\ BALB/c matings were enhanced from 6 to 44% and 55%. Lipopolysaccharride (LPS), which is known to lead to the release of TNF-\g=a\, had a similar effect, leading to gestational age-and dose-dependent enhancement of resorptions up to 100%.However, cytokines of the CSF family, including IL-3 and GM-CSF, increased the chances of fetal survival when injected into abortion-prone mice, e.g. reducing resorption rates in the abortion-prone CBA/J \m=x\ DBA/2 mating combination from 55 to 22% (IL-3), and 47 to 8% (GM-CSF). They also increased fetal and placental weight and, in particular, expanded the spongiotrophoblast zone in the placenta. The latter observations may be due to a direct trophic influence on placental cells, perhaps through a cytokine cascade, or an indirect effect due to inhibition of natural killer (NK)-like cells, or both. Whatever the mechanism, these results may find practical application in influencing reproductive outcome in women and other species.

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Infiltrating decidual natural killer cells are associated with spontaneous abortion in mice

Cited by 173 publications

References 12 publications

Embryonic Resorption and Polycyclic Aromatic Hydrocarbons: Putative Immune-mediated Mechanisms

Embryonic Resorption and Polycyclic Aromatic Hydrocarbons: Putative Immune-mediated Mechanisms

Sex-Associated Hormones and Immunity to Protozoan Parasites

Control of fetal survival in CBA x DBA/2 mice by lymphokine therapy

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