Natural Killer Cells Are Characterized by the Concomitantly Increased Interferon-γ and Cytotoxicity in Acute Resolved Hepatitis B Patients

Interferon-γ (IFN-γ), a cytokine produced by activated natural killer cells and T lymphocytes, is an important regulator of innate and adaptive immunity. Interleukin (IL)-18, also known as IFN-γ-inducing factor, is a cytokine that induces T and natural killer cells to produce IFN-γ. In this study, the chicken IL-18 (ChIL-18) and chicken IFN-γ (ChIFN-γ) genes were inserted into the pET28a prokaryotic expression vector, resulting in pET28a-IL-18 and pET28a-IFN-γ, respectively. These plasmids were transformed into Escherichia coli strain BL21, and the ChIL-18 and ChIFN-γ proteins were expressed and purified. To determine their antiviral activities, 200 ng/mL of ChIL-18 and/or ChIFN-γ were inoculated into chicken embryonic fibroblast cells. After 24 h, one 50% tissue culture infective dose (TCID50) of infectious bursal disease virus (IBDV) was inoculated into the chicken embryonic fibroblast cells. The results showed that the antiviral effect of ChIL-18 and ChIFN-γ in combination was better than that of ChIL-18 or ChIFN-γ alone. Next, 14-day-old chicken were injected with 200 µg of ChIL-18 and/or ChIFN-γ and then were challenged with 103 TCID50 of IBDV via intraperitoneal injection. The results showed that the proliferation of IBDV was inhibited by the injection of the recombinant proteins, especially the combination of ChIL-18 and ChIFN-γ, as evidenced by cytokine detection, quantitative PCR, and pathology analyses. These results indicate that ChIL-18 and ChIFN-γ could inhibit IBDV infection and the combination of ChIL-18 and ChIFN-γ has a better inhibitory effect than either cytokine alone.

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A Novel Pro-Angiogenic Function for Interferon-γ–Secreting Natural Killer Cells

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.14-14093 ◽

2014 ◽

Vol 55 (5) ◽

pp. 2885 ◽

Cited By ~ 20

Author(s):

HyunSoo Lee ◽

Simona L. Schlereth ◽

Eun Y. Park ◽

Parisa Emami-Naeini ◽

Sunil K. Chauhan ◽

...

Keyword(s):

Natural Killer Cells ◽

Natural Killer ◽

Interferon Γ ◽

Killer Cells

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Expression of interferon-γ in decidual natural killer cells from women with hypertensive disorder complicating pregnancy

Journal of Obstetrics and Gynaecology Research ◽

10.1111/jog.12216 ◽

2013 ◽

Vol 40 (3) ◽

pp. 670-676 ◽

Cited By ~ 11

Author(s):

Juan Zhou ◽

Xiao-Min Xiao ◽

Ying-Hua Wu

Keyword(s):

Natural Killer Cells ◽

Natural Killer ◽

Interferon Γ ◽

Hypertensive Disorder ◽

Killer Cells ◽

Hypertensive Disorder Complicating Pregnancy ◽

Decidual Natural Killer Cells

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Production of interferon-γ by natural killer cells and aging in chronic human schistosomiasis

Mediators of Inflammation ◽

10.1080/09629350400008802 ◽

2004 ◽

Vol 13 (5-6) ◽

pp. 327-333 ◽

Cited By ~ 10

Author(s):

E. Speziali ◽

J. Bethony ◽

O. Martins-Filho ◽

L. A. O. Fraga ◽

D. S. Lemos ◽

...

Keyword(s):

Natural Killer Cells ◽

Natural Killer ◽

Infection Intensity ◽

The Elderly ◽

Interferon Γ ◽

Older Individuals ◽

Killer Cells ◽

Human Schistosomiasis ◽

Ifn Γ

BACKGROUNG: Aging is associated with several alterations in the phenotype, repertoire and activation status of lymphocytes as well as in the cytokine profile produced by these cells. As a lifelong condition, chronic parasitic diseases such as human schistosomiasis overlaps with the aging process and no systematic study has yet addressed the changes in immune response during infection withSchistosoma mansoniin older individuals.Aim: Herein we study the influence of immunological alterations brought about by senescence in the course of schistosomiasis.Materials and methods: Individuals 10-95 years of age, from both sexes, from an endemic area forS. mansoniinfection were matched by intensity of infection as measured by egg counts. We analyzed, as a parameter, cytokine expression by lymphocytes and natural killer cells afterin vitrostimulation with soluble egg antigen and soluble worm antigen using flow cytometry.Results: We demonstrated that the frequency of CD16+interferon-γ (IFN-γ)+natural killer cells in negative individuals over the age of 70 years is significantly higher than in positive individuals afterin vitrostimulation withS. mansoniantigen extracts. The frequency of these cells is increased in all individuals over the age of 50 years and only declines in positive individuals after 70 years of age. Analysis of either CD4?or CD8?cells after antigen stimulation show no significant increase in frequency of IFN-γ in negative or in positive individuals of this age group, suggesting that the effect on CD16+cells is not T-cell dependent.Conclusion: Since production of IFN-γ has been related to resistance to schistosome infection, our data suggest that age-associated changes in CD16+cells may play a role in controlling infection intensity in the elderly inS. mansoniendemic areas of Brazil.

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Systemic hypoxia affects exercise-mediated antitumor cytotoxicity of natural killer cells

Journal of Applied Physiology ◽

10.1152/japplphysiol.00687.2009 ◽

2009 ◽

Vol 107 (6) ◽

pp. 1817-1824 ◽

Cited By ~ 10

Author(s):

Jong-Shyan Wang ◽

Chia-Kuan Wu

Keyword(s):

Natural Killer Cells ◽

Natural Killer ◽

Granzyme B ◽

Interferon Γ ◽

Moderate Intensity ◽

Hypoxic Exposure ◽

Dependent Manner ◽

Killer Cells ◽

Peripheral Tissues ◽

Systemic Hypoxia

Natural killer cells (NKs) are important to the clearance of transformed cells. This investigation elucidates how systemic hypoxia influences mobilization of the NK subsets and cytotoxicity of NKs to nasopharyngeal carcinoma cells (NPCs) during exercise. Sixteen sedentary men performed six distinct experimental tests in an air-conditioned normobaric hypoxia chamber: high-intensity exercise [HE; up to maximal O2 consumption (V̇o2 max)] under 21% O2; moderate-intensity exercise (ME; 50% V̇o2 max for 30 min) under 12%, 15%, and 21% O2; and breathing 12% and 15% O2 for 30 min at rest. The results demonstrated that 21% O2 HE, but not ME, increased cellular perforin/granzyme B/interferon-γ levels in NKs and interferon-γ concentration in NK-NPC coincubation, and also promoted capacity of NKs to bind to NPCs and NK-induced CD95 expression and phosphatidylserine exposure of NPCs. However, the HE simultaneously increased percentages of the replicative senescent (CD57+ and CD28−) NKs and the NKs with inhibitory receptors (KLRG1+) that entered the bloodstream from peripheral tissues. Breathing 12% and 15% O2 at rest did not influence mobilization of NK subsets and cytotoxicity of NKs to NPCs. Although both 12% and 15% O2 ME increased NK count, perforin/granzyme B/interferon-γ levels, NK-NPC binding, and NK-induced CD95 expression and apoptosis of NPC, only 12% O2 ME increased percentages of the NKs with CD57+/CD28−/KLRG1+ in blood. Therefore, we conclude that systemic hypoxic exposure affects redistribution of NK subsets and anti-NPC cytotoxicity of NKs during exercise in a concentration-dependent manner. Moreover, exposure to 12% O2 promotes the NK cytotoxicity with mobilizing the replicative senescent/inhibitory NKs into the bloodstream during ME.

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