Natural killer cell stimulatory factor (NKSF) or interleukin-12 is a key regulator of immune response and inflammation

Trinchieri, Giorgio; Wysocka, Maria; D’Andrea, Annalisa; Rengaraju, Manthrasalam; Aste-Amézaga, Miguel; Kubin, Marek; Valiante, Nicholas M.; Chehimi, Jihed

doi:10.1016/0955-2235(92)90016-b

Cited by 152 publications

(95 citation statements)

References 36 publications

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“…Four Th1 and two Th0 clones were kept in culture with IL-2 to analyse their phenotype stability. It has been shown that IL-2 can increase IFN␥ production in T cells [33], although it cannot direct the development of their Th1 or Th2 phenotype. All the Th1/Th0 clones had stable phenotypes although their level of cytokine production varied.…”

Section: Discussionmentioning

confidence: 99%

Change in the Th1/Th2 Phenotype of Memory T‐Cell Clones from Rheumatoid Arthritis Synovium

Aarvak¹,

Chabaud

Källberg³

et al. 1999

Scand J Immunol

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The stability of established memory T helper (Th)1/Th2 cells in chronic inflammatory diseases is not clear, and a shift of the cytokine balance could control chronic inflammation. In order to study the regulation of the Th phenotype of memory T cells, polyclonal T‐cell lines and clones with a Th1, Th0 or Th2 phenotype were developed from rheumatoid synovial tissue. Th1 [interleukin (IL)‐12 + anti‐IL‐4] and Th2 (IL‐4 + anti‐IL‐12) promoting environments and IL‐2 were used to manipulate the cytokine profile. Polyclonal T‐cell lines of predominantly Th1 type could be shifted to produce Th2 cytokines, and polyclonal Th2/Th0 lines could be shifted to produce Th1 cytokines. However, this shift was due to an amplification of CD8+ T cells with a memory phenotype and a loss of the CD4+ T cells, giving Tc2 or Tc1 profiles, respectively. Th2 clones cultured repeatedly with IL‐2 switched to either a Th0 or a Th1 phenotype, while both Th1 and Th0 memory clones kept a stable phenotype. Addition of Th2‐promoting conditions strongly reduced the production of both interferon‐gamma and IL‐17, while Th1‐promoting conditions increased the production of these cytokines. These results demonstrate that RA Th2 clones readily switch, while Th1 and Th0 clones are stable. However, induction of Th2 cytokines can be obtained in polyclonal polarized memory T cells due to amplification of Tc2 cells.

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Section: Discussionmentioning

confidence: 99%

Change in the Th1/Th2 Phenotype of Memory T‐Cell Clones from Rheumatoid Arthritis Synovium

Aarvak¹,

Chabaud

Källberg³

et al. 1999

Scand J Immunol

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“…IL-12 p70 has been shown to be a strong inducer of IFNc leading to protection from bacterial infections [20,21,21]. Our recent studies demonstrated that although IL-12/23 p40 is produced readily upon Francisella infection of PBM, there was no detectable IL-12 p70 [10].…”

Section: Ifnc-primed Monocytes Produce Il-12 P70mentioning

confidence: 99%

IFNγ enhances IL‐23 production during Francisella infection of human monocytes

Butchar¹,

Parsa²,

Marsh³

et al. 2008

FEBS Letters

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We previously demonstrated that monocytes produce IL-23 during Francisella infection, and that IL-23 induces IFNc from NK cells. Here, we demonstrate that IFNc-priming of monocytes enhances IL-23 production during Francisella infection. This effect was seen on the IL12/23 p40 subunit. Induction of IL-12/23 p40 is reported to be enhanced by IRF-1 and IRF-8. Consistently, microarray analysis of IFNc-treated monocytes revealed a significant induction of the IRFs. Interestingly, IFNcprimed monocytes produced IL-12 p70, a more potent inducer of IFNc than IL-23. We propose that there exists an amplification loop between monocyte IL-23 and NK/T cell IFNc that leads to IL-12 p70 production.

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“…Three of these critical modulators are the cytokines IL-12 (40), TNF-␣ (41, 42), and IFN-␣ (5, 41). Incubation of NK cells with IL-12, TNF-␣, and IFN-␣ has been shown to result in the activation and enhancement of the cytolytic potential of NK cells (43)(44)(45). To determine whether IL-12, TNF-␣, and/or IFN-␣ secretion by pDCs or monocytes in response to ssRNA40 stimulation through TLR7/8 mediated the activation of NK cells, we incubated purified NK cells with 3M002, ssRNA40/Dotap, ssRNA41/Dotap, Dotap alone, or medium alone in the presence or absence of IL-12, TNF-␣, and/or IFN-␣, and compared this with the NK cell activation in bulk PBMC.…”

Section: Nk Cells Require Direct Cell-to-cell Contact With Pdcs and Mmentioning

confidence: 99%

Single-Stranded RNA Derived from HIV-1 Serves as a Potent Activator of NK Cells

Alter

Suscovich

Teigen

et al. 2007

The Journal of Immunology

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Persistent immune activation is a hallmark of chronic viremic HIV-1 infection. Activation of cells of the innate immune system, such as NK cells, occurs rapidly upon infection, and is sustained throughout the course of the disease. However, the precise underlying mechanism accounting for the persistent HIV-1-induced activation of NK cells is poorly understood. In this study, we assessed the role of uridine-rich ssRNA derived from the HIV-1 long terminal repeat (ssRNA40) on activation of NK cells via TLR7/8. Although dramatic activation of NK cells was observed following stimulation of PBMC with ssRNA40, negligible activation was observed following stimulation of purified NK cells despite their expression of TLR8 mRNA and protein. The functional activation of NK cells by this HIV-1-encoded TLR7/8 ligand could not be reconstituted with exogenous IL-12, IFN-α, or TNF-α, but was critically dependent on the direct contact of NK cells with plasmacytoid dendritic cells or CD14+ monocytes, indicating an important level of NK cell cross-talk and regulation by accessory cells during TLR-mediated activation. Coincubation of monocyte/plasmacytoid dendritic cells, NK cells, and ssRNA40 potentiated NK cell IFN-γ secretion in response to MHC-devoid target cells. Studies using NK cells derived from individuals with chronic HIV-1 infection demonstrated a reduction of NK cell responsiveness following stimulation with TLR ligands in viremic HIV-1 infection. These data demonstrate that HIV-1-derived TLR ligands can contribute to the immune activation of NK cells and may play an important role in HIV-1-associated immunopathogenesis and NK cell dysfunction observed during acute and chronic viremic HIV-1 infection.

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Natural killer cell stimulatory factor (NKSF) or interleukin-12 is a key regulator of immune response and inflammation

Cited by 152 publications

References 36 publications

Change in the Th1/Th2 Phenotype of Memory T‐Cell Clones from Rheumatoid Arthritis Synovium

Change in the Th1/Th2 Phenotype of Memory T‐Cell Clones from Rheumatoid Arthritis Synovium

IFNγ enhances IL‐23 production during Francisella infection of human monocytes

Single-Stranded RNA Derived from HIV-1 Serves as a Potent Activator of NK Cells

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