Monoclonal Antibodies to the Human Interferon-γ Receptor: Blocking of the Biological Activities of Interferon-γ and Purification of the Receptor

Novick, Daniela; Fischer, Dina G.; Reiter, Zvi; Eshhar, Zelig; Rubinstein, Menachem

doi:10.1089/jir.1989.9.315

Cited by 19 publications

(13 citation statements)

References 23 publications

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“…These effects are thought to be mediated by a cell surface receptor (Aguet, 1980) which does not bind IFN-a or IFN-/3 (Branca and Baglioni, 1981). The human IFN-y receptor has been purified and characterized from a biochemical point of view showing a molecular weight of around 9(I,000 (Novick et al, 1987(Novick et al, , 1989. Monoclonal antibodies with the ability to block the binding of I25I-labeled IFN-,/to its receptor have been raised against it (Novick et al, 1989;Depla and De Ley, 1990).…”

Section: Discussionmentioning

confidence: 99%

Demonstration of the presence of a specific interferon-γ receptor on murine astrocyte cell surface

Rubio¹,

Felipe²

1991

Journal of Neuroimmunology

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Interferon gamma (IFN-gamma) is a pleiotropic lymphokine produced by T-lymphocytes which acts as a soluble mediator in immunological reactions. In addition to several immune target cells, such as monocytes and macrophages, it acts on the principal glial population, the astrocytes, inducing Ia antigen expression. We have developed a binding assay for 125I-labeled recombinant murine IFN-gamma, and show that, using this assay, IFN-gamma interacts with a single specific receptor on the murine astrocyte cell membrane. The binding is specific and saturable and it takes place with a Kd = 1.64 x 10(-9) M, with 11,100 receptor molecules per astrocytic cell. The binding shows, as for macrophages, species specificity. Using an immune assay including rabbit antibodies to IFN-gamma and 125I-labeled protein A, we have demonstrated an internalization of the ligand. This is an energy-dependent process, as around 50% of the bound IFN-gamma is endocytosed after 4 h at 37 degrees C when cultures are maintained in complete culture medium.

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Section: Discussionmentioning

confidence: 99%

Demonstration of the presence of a specific interferon-γ receptor on murine astrocyte cell surface

Rubio¹,

Felipe²

1991

Journal of Neuroimmunology

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“…They were then incubated with biotinylated rat anti-mouse antibody (Immunotech, Marseilles, France) and streptavidin-phycoerythrin (Tebu, Le Perray en Yvelines, France). Antibody GIR94 is IgG2b (Genzyme Pharmaceuticals, Cambridge, Massachusetts, USA) (18) and other specific antibodies are IgG1 and include 21/31.1 (Valbiotech, Paris, France), GIR208 (Genzyme) (18), γR38 and γR99 (19), A6 (20), 177.1 (21), and IRγ2 (22). All antibodies were independent, and all but one (GIR94) were blocking antibodies.…”

Section: Methodsmentioning

confidence: 99%

In a novel form of IFN-γ receptor 1 deficiency, cell surface receptors fail to bind IFN-γ

Jouanguy¹,

Dupuis²,

Pallier³

et al. 2000

J. Clin. Invest.

150

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“…Therefore, we blocked IFN-␥ activity using a mAb to the IFN-␥ receptor (anti-IFN-␥R, previously described in Ref. 23). As shown in Fig.…”

Section: Modulation Of the Bioactivity Of Ifn-␥ In Pmbc Cultures Affementioning

confidence: 99%

Endogenous IL-32 Controls Cytokine and HIV-1 Production

Nold

Nold-Petry

Pott

et al. 2008

The Journal of Immunology

114

148

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IL-32, a proinflammatory cytokine that activates the p38MAPK and NF-κB pathways, induces other cytokines, for example, IL-1β, IL-6, and TNF-α. This study investigated the role of endogenous IL-32 in HIV-1 infection by reducing IL-32 with small interfering (si)RNA in freshly infected PBMC and in the latently infected U1 macrophage cell line. When PBMC were pretreated with siRNA to IL-32 (siIL-32), IL-6, IFN-γ, and TNF-α were reduced by 57, 51, and 36%, respectively, compared with scrambled siRNA. Cotransfection of NF-κB and AP-1 reporter constructs with siIL-32 decreased DNA binding of these transcription factors by 42 and 46%, respectively. Cytokine protein array analysis revealed that the inhibitory activity of siIL-32 primarily targeted Th1 and proinflammatory cytokines and chemokines, e.g., MIP-1α/β. Unexpectedly, HIV-1 production (as measured by p24) increased 4-fold in these same PBMC when endogenous IL-32 was reduced. Because IFN-γ was lower in siIL-32-treated PBMC, we blocked IFN-γ bioactivity, which enhanced the augmentation of p24 by siIL-32. Furthermore, siIL-32 reduced the natural ligands of the HIV-1 coreceptors CCR5 (MIP-1α/β and RANTES) and CXCR4 (SDF-1). Inhibition of endogenous IL-32 in U1 macrophages also increased HIV-1. When rhIL-32γ was added to these cells, p24 levels fell by 72%; however, in the same cultures IFN-α increased 4-fold. Blockade of IFN-α/β bioactivity in IL-32γ-stimulated U1 cells revealed that IFN-α conveys the anti-HIV-1 effect of rhIL-32γ. In summary, depletion of endogenous IL-32 reduced the levels of Th1 and proinflammatory cytokines but paradoxically increased p24, proposing IL-32 as a natural inhibitor of HIV-1.

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Monoclonal Antibodies to the Human Interferon-γ Receptor: Blocking of the Biological Activities of Interferon-γ and Purification of the Receptor

Cited by 19 publications

References 23 publications

Demonstration of the presence of a specific interferon-γ receptor on murine astrocyte cell surface

Demonstration of the presence of a specific interferon-γ receptor on murine astrocyte cell surface

In a novel form of IFN-γ receptor 1 deficiency, cell surface receptors fail to bind IFN-γ

Endogenous IL-32 Controls Cytokine and HIV-1 Production

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