Response of resting human peripheral blood natural killer cells to interleukin 2.

Trinchieri, Giorgio; Matsumoto-Kobayashi, M; Clark, SC; Seehra, Jasbir; London, Lucille; Perussia, Bice

doi:10.1084/jem.160.4.1147

Cited by 565 publications

(240 citation statements)

References 53 publications

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“…The cytokine network is hence sufficiently established by IFN -production originating from Th1 cells. Nevertheless, NK cells, which predominantly contribute to the early production of IFN -in response to IL -12, 66 are necessary for its full activation. In addition, (3 ) the feedback loop is interrupted in IFN -receptor± deficient mice as evidenced by IL -12 serum levels below 1 ng /mL despite profound IFN -production upon IL-12 DNA injection.…”

Section: Discussionmentioning

confidence: 99%

Induction of long-lasting cytokine effect by injection of IL-12 encoding plasmid DNA

et al. 2000

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We have recently demonstrated that DNA coding for both subunits of the murine IL -12 heterodimer exhibits a strong antimetastatic effect against B16 -melanoma in C57BL / 6 mice and after intratumoral injection tumor regression. Here we show that the antimetastatic effect can be detected when the DNA is injected intramuscularly 30 days before tumor cell challenge. A long -term IL -12 expression was measured for up to 50 days in the serum with a peak at day 20 amounting to about 10 ng / mL in C57BL / 6 mice. CpG oligodeoxynucleotides also induce IL -12 expression, however, only for a few hours. IL -12 DNA administration induces longlasting systemic IFN -production, whereas IL -4 and TNF -levels remained undetectable. NK cell ± depleted mice showed a strong but reduced expression of murine IL -12. Expression of DNA encoding human instead of murine IL -12 resulted in a significantly lower and transient expression, indicating that not plasmid -derived IL -12 production alone but the immune system of the host contributes to the long -lasting antimetastatic effect. It may be attributable to an autocrine feedback mechanism maintaining murine IL -12 expression, whereby several cell populations including NK cells are involved. Cancer Gene Therapy ( 2000 ) 7, 1557 ± 1565

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Section: Discussionmentioning

confidence: 99%

Induction of long-lasting cytokine effect by injection of IL-12 encoding plasmid DNA

et al. 2000

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“…A major source of IFN-within the population of human leucocytes is NK cells, a subset of lymphocytes with CD3 -/56 + phenotype that constitutively kill tumour cells without apparent restriction by histocompatibility molecules [2]. Resting human NK cells carry the p70 moiety of the IL-2R [3] and respond to IL-2 by induction of IFN-production [4,5] as well as enhanced cytolytic activity and proliferation [5].…”

Section: Introductionmentioning

confidence: 99%

Histaminergic regulation of interferon-gamma (IFN-γ) production by human natural killer (NK) cells

Asea¹,

Hansson²,

Czerkinsky³

et al. 1996

Clinical and Experimental Immunology

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SUMMARYMonocytes, recovered from human peripheral blood by counter-current centrifugal elutriation, effectively inhibit the production of IFN-°by CD3 ÿ /56 NK cells in response to IL-2. This study aimed at defining the nature of the inhibitory signal, particularly the importance of monocyte-derived reactive metabolites of oxygen. It was found that monocytes recovered from patients with chronic granulomatous disease (CGD), a condition characterized by deficient NADPH-oxidase activity of phagocytes, did not inhibit IFN-°production by NK cells. Further, catalase, a scavenger of hydrogen peroxide, completely reversed the inhibitory signal, whereas scavengers of the superoxide anion, hypohalous acids, the hydroxyl radical, or nitric oxide synthesis inhibitors such as L-NMMA were ineffective. Inhibition of IFN-°production was operating on a pre-translational level, as indicated by the inability of enriched NK cells to accumulate IFN-°mRNA in the presence of elutriated monocytes. Hydrogen peroxide, at micromolar concentrations, reconstituted the inhibition of IFN-°production when added to enriched NK cells. Histamine, a biogenic amine which inhibits the generation of reactive oxygen metabolites in monocytes, abrogated the inhibition of IFN-°production in NK cells; by this mechanism, histamine strongly synergized with IL-2 to induce IFN-°in mixtures of NK cells and monocytes. The synergizing effect of histamine was specifically mediated by H 2 -type histamine receptors. We conclude that: (i) the induction of IFN-°mRNA in NK cells is effectively down-regulated by products of the oxidative metabolism of monocytes; and (ii) histamine effectively enhances IFN-°production by preventing monocyte-induced oxidative damage to NK cells.

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“…Mature peripheral blood natural killer (NK) cells, similar to lymphocytes, retain some proliferative capacity 11 . NK cells participate in the control of viral or bacterial infection, regulation of hematopoiesis, production of cytokines and cytotoxicity of neoplastic cells.…”

Section: Introductionmentioning

confidence: 99%

Neonates born to pre-eclamptic mothers have a higher percentage of natural killer cells (CD3 - /CD56+16+) in umbilical cord blood than those without pre-eclampsia

White

Ahlstrand²

2003

DJMF

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Objective: Maternal endothelial dysfunction and intravascular inflammation have been implicated in the mechanisms of disease responsible for the clinical syndrome of pre-eclampsia. Recently, the activation of the innate limb of the immune response (neutrophils and monocytes) in the fetal circulation has been reported in neonates born to mothers with pre-eclampsia. Natural killer (NK) cells are identified morphologically as a subpopulation of lymphocytes, but functionally as one component of the innate immune system. NK cells participate in the control of viral or bacterial infection, regulation of hematopoiesis, production of cytokines and cytotoxicity of neoplastic cells. Accumulating evidence suggests that the innate system is required for mounting an adequate adaptive response. NK cells, originally defined as effector cells of the innate immune system, may also play a role as regulatory cells for the adaptive immune system. This study was designed to determine the proportion of the NK cell subset of lymphocytes in umbilical cord blood of neonates born to mothers with and without pre-eclampsia. Methods: A cross-sectional study including neonates of mothers with (n = 48) and those without pre-eclampsia (control group) (n = 72) was conducted. Pre-eclampsia was diagnosed in the presence of hypertension and proteinuria. The control group consisted of neonates (premature and term) with no evidence of acute inflammation within the extraplacental membranes (chorioamnionitis). Umbilical cord blood was collected at the time of delivery, and assayed using monoclonal antibodies for selective cluster differentiation (CD) antigens in order to determine the proportion of NK cells as a percentage of total lymphocytes. The immunophenotypic characteristic was determined using flow cytometry, and NK cells were identified by positivity of CD16 and CD56 without CD3 (CD3-/CD56+16+). Log transformation of the percentage of NK cells was performed. Parametric statistics were used for analysis. Multiple regression analysis was utilized to examine the contribution of potentially confounding factors on the proportion of NK cells. A p value of < 0.05 was considered statistically significant. Results: Neonates born to mothers with pre-eclampsia had a significantly higher percentage of NK cells (CD3-/CD56+16+) than those in the control group (pre-eclampsia, mean ± SD 17 ± 9% vs. control, mean ± SD 12 ± 7.5%; p = 0.001). Multiple regression analysis suggested that umbilical cord blood pH of < 7.2, labor with vaginal delivery and maternal pre-eclampsia were associated with an increased percentage of NK cells in umbilical cord blood. Conclusions: Pre-eclampsia is associated with a higher NK cell (CD3-/CD56+16+) subset of lymphocytes in umbilical cord blood than in the control group. This difference cannot be explained by fetal acidosis or the presence of labor.

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Response of resting human peripheral blood natural killer cells to interleukin 2.

Cited by 565 publications

References 53 publications

Induction of long-lasting cytokine effect by injection of IL-12 encoding plasmid DNA

Induction of long-lasting cytokine effect by injection of IL-12 encoding plasmid DNA

Histaminergic regulation of interferon-gamma (IFN-γ) production by human natural killer (NK) cells

Neonates born to pre-eclamptic mothers have a higher percentage of natural killer cells (CD3 - /CD56+16+) in umbilical cord blood than those without pre-eclampsia

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