Cytokine production in natural killer cells and lymphocytes in pregnant women compared with women in the follicular phase of the ovarian cycle

Nieuwenhoven, Angelique L. Veenstra van; Bouman, Annechien; Moes, Hendrik; Heineman, M. J.; Leij, Lou F. M. H. de; Santema, Job G.; Faas, Marijke M.

doi:10.1016/s0015-0282(02)02976-x

Cited by 114 publications

(88 citation statements)

References 25 publications

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“…However, our own data demonstrate different responses based on the stimulation condition: the increase in MIP-1β production was observed only after infection of PBMC cultures with pH1N1 virus, and less so with H3N2 virus, but not with generalized stimulation with PMA/I. This difference is a critical distinction because nearly all in vitro evidence reporting decreased NK-and T-cell function during pregnancy has relied on such nonspecific stimulation (15,16), which our data also demonstrate. The inflammatory response to pH1N1 and H3N2 virus was also very different, with higher frequencies of IFN-γ-producing cells after H3N2 infection but lower T-cell production of MIP-1β.…”

Section: Discussionmentioning

confidence: 52%

“…For instance, suppression of T-cell and natural killer (NK)-cell responses by regulatory T cells during pregnancy is linked to amelioration of certain autoimmune diseases (10)(11)(12). In addition, NK and T cells from pregnant women exhibit decreased interferon (IFN)-γ and macrophage inflammatory protein (MIP)-1β production in response to interleukin (IL)-12/15 stimulation or phorbol 12-myristate 13-acetate and ionomycin (PMA/I) (13)(14)(15)(16). Prior work has also suggested a systemic type 2 T helper (Th2) bias as pregnancy progresses (17,18).…”

mentioning

confidence: 99%

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Enhanced natural killer-cell and T-cell responses to influenza A virus during pregnancy

Kay¹,

Fukuyama²,

Aziz

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Pregnant women experience increased morbidity and mortality after influenza infection, for reasons that are not understood. Although some data suggest that natural killer (NK)-and T-cell responses are suppressed during pregnancy, influenza-specific responses have not been previously evaluated. Thus, we analyzed the responses of women that were pregnant (n = 21) versus those that were not (n = 29) immediately before inactivated influenza vaccination (IIV), 7 d after vaccination, and 6 wk postpartum. Expression of CD107a (a marker of cytolysis) and production of IFN-γ and macrophage inflammatory protein (MIP) 1β were assessed by flow cytometry. Pregnant women had a significantly increased percentage of NK cells producing a MIP-1β response to pH1N1 virus compared with nonpregnant women pre-IIV [median, 6.66 vs. 0.90% (P = 0.0149)] and 7 d post-IIV [median, 11.23 vs. 2.81% (P = 0.004)], indicating a heightened chemokine response in pregnant women that was further enhanced by the vaccination. Pregnant women also exhibited significantly increased T-cell production of MIP-1β and polyfunctionality in NK and T cells to pH1N1 virus pre-and post-IIV. NK-and T-cell polyfunctionality was also enhanced in pregnant women in response to the H3N2 viral strain. In contrast, pregnant women had significantly reduced NK-and T-cell responses to phorbol 12-myristate 13-acetate and ionomycin. This type of stimulation led to the conclusion that NK-and T-cell responses during pregnancy are suppressed, but clearly this conclusion is not correct relative to the more biologically relevant assays described here. Robust cellular immune responses to influenza during pregnancy could drive pulmonary inflammation, explaining increased morbidity and mortality.

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Section: Discussionmentioning

confidence: 52%

mentioning

confidence: 99%

Enhanced natural killer-cell and T-cell responses to influenza A virus during pregnancy

Kay¹,

Fukuyama²,

Aziz

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…It has been reported that populations of peripheral blood IL-10-producing (NKr1)-CD56 bright and CD56 dim NK cells in early pregnancy women were increased compared with spontaneous abortion cases (43). Veenstra van Nieuwenhowen et al (44) reported a mild increase in the IL-10 production of blood NK cells in pregnancy, and these findings suggest that regulatory NK cells in peripheral blood and in deciduas of early pregnancy might play some important roles in the maintenance of pregnancy by the regulation of maternal immune function.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, IL-10 down-regulates the Ag-presenting capacity, such as HLA-DR expression, costimulatory molecules, and several cytokines in dendritic cells and monocytes/macrophages (51). Various studies have suggested that the timing and possibly the localization of IL-10 production critically affects its immune regulatory functions (35,(43)(44)(45)(51)(52)(53). Taken together, direct purification of IL-10-secreting and nonsecreting NK cell subsets from peripheral blood of healthy individuals enabled to demonstrate the in vivo existence of a regulatory NK cell subset, which may play an immune regulatory and suppressor role.…”

Section: Discussionmentioning

confidence: 99%

Regulatory NK Cells Suppress Antigen-Specific T Cell Responses

Deniz

Erten

Küçüksezer

et al. 2008

The Journal of Immunology

226

147

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The immune system has a variety of regulatory/suppressive processes, which are decisive for the development of a healthy or an allergic immune response to allergens. NK1 and NK2 subsets have been demonstrated to display counterregulatory and provocative roles in immune responses, similar to Th1 and Th2 cells. T regulatory cells suppressing both Th1 and Th2 responses have been the focus of intensive research during the last decade. In this study, we aimed to investigate regulatory NK cells in humans, by characterization of NK cell subsets according to their IL-10 secretion property. Freshly purified IL-10-secreting NK cells expressed up to 40-fold increase in IL-10, but not in the FoxP3 and TGF-β mRNAs. PHA and IL-2 stimulation as well as vitamin D3/dexamethasone and anti-CD2/CD16 mAbs are demonstrated to induce IL-10 expression in NK cells. The effect of IL-10+ NK cells on Ag-specific T cell proliferation has been examined in bee venom major allergen, phospholipase A2- and purified protein derivative of Mycobecterium bovis-induced T cell proliferation. IL-10+ NK cells significantly suppressed both allergen/Ag-induced T cell proliferation and secretion of IL-13 and IFN-γ, particularly due to secreted IL-10 as demonstrated by blocking of the IL-10 receptor. These results demonstrate that a distinct small fraction of NK cells display regulatory functions in humans.

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“…In addition, NK cells show decreased production of IFN-γ (Veenstra van Nieuwenhoven et al, 2002) and a shift towards a Th2-associated phenotype has been proposed (Borzychowski et al, 2005).…”

Section: Innate Immune Cellsmentioning

confidence: 99%

Immune regulation at the fetal‐maternal interface with focus on decidual macrophages

Svensson‐Arvelund¹

2015

Linköping University Medical Dissertations

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A successful pregnancy requires that the maternal immune system adapts to tolerate the semi-allogeneic fetal-placental unit. This adaptation mainly occurs locally, i.e. at the fetal-maternal interface, where fetal-derived tissues come into close contact with maternal cells in the uterine endometrium (called decidua during pregnancy). decidual macrophages preferentially secreted the monocyte-and Treg cell-associated chemokines CCL2 and CCL18, while Th1-, Th2-and Th17-related chemokines were produced at low levels. These results suggest that decidual macrophages contribute to create the unique decidual cell composition and a tolerogenic immune environment that is compatible with fetal development. Further, by comparing decidual macrophages with different in vitro macrophage subsets, we showed that M-CSF and

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Cytokine production in natural killer cells and lymphocytes in pregnant women compared with women in the follicular phase of the ovarian cycle

Cited by 114 publications

References 25 publications

Enhanced natural killer-cell and T-cell responses to influenza A virus during pregnancy

Enhanced natural killer-cell and T-cell responses to influenza A virus during pregnancy

Regulatory NK Cells Suppress Antigen-Specific T Cell Responses

Immune regulation at the fetal‐maternal interface with focus on decidual macrophages

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