Monoclonal antibody to murine gamma interferon inhibits lymphokine-induced antiviral and macrophage tumoricidal activities.

Spitalny, George L.; Havell, Edward A.

doi:10.1084/jem.159.5.1560

Cited by 345 publications

(116 citation statements)

References 12 publications

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“…The concentration of interferon-␥ (IFN␥) was determined by ELISA in the culture medium collected after 72 hours of stimulation. Microtiter plates were coated with 5 g/ml anti-mouse IFN␥ mAb (clone R4-6A2 [64]). After blocking with 1% BSA, the plates were incubated with IFN␥ standard (from 20 ng/ml; PharMingen, San Diego, CA) and supernatants from cell cultures.…”

mentioning

confidence: 99%

Soluble complement receptor 1 (CD35) delivered by retrovirally infected syngeneic cells or by naked DNA injection prevents the progression of collagen-induced arthritis

Dreja¹,

Annenkov

Chernajovsky

2000

Arthritis & Rheumatism

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Objective. The complement system is important in the development of autoimmune inflammation, including rheumatoid arthritis (RA) and collagen-induced arthritis (CIA). Complement receptor 1 (CR1) is involved in regulation of complement activity. Studies on models of autoimmunity have demonstrated that soluble CR1 (sCR1) is a potent therapeutic agent. The present study was thus undertaken to investigate the feasibility of antiinflammatory gene therapy to prevent CIA by delivery of genes encoding truncated sCR1 (tsCR1) and dimeric tsCR1-Ig.Methods. Syngeneic fibroblasts or arthritogenic splenocytes, engineered to express tsCR1 using retrovirus-mediated gene transfer, were injected into DBA/1 recipients that had been immunized with bovine type II collagen (CII). In separate experiments, naked DNA containing tsCR1 and tsCR1-Ig genes was injected intramuscularly into the immunized animals. The clinical development of arthritis was monitored, anti-CII levels measured, and antigenic T cell response studied. Affinity-purified tsCR1-Ig was assayed for its inhibitory effect on the alternative complement pathway in mouse serum.Results. Treatment of CII-immunized mice with the tsCR1-expressing cells inhibited development of CIA, reduced anti-CII antibody levels, and inhibited T cell response to CII in vitro. Intramuscular injections of DNA encoding the CR1 genes prevented the progression of disease. Furthermore, compared with full-length sCR1, purified tsCR1-Ig was more active in inhibiting the murine alternative complement pathway.Conclusion. Our findings demonstrated that tsCR1 and tsCR1-Ig, when delivered via gene therapy, had a beneficial effect on autoimmune inflammation. These results indicate that targeting the complement system in RA patients may be of clinical importance.

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confidence: 99%

Soluble complement receptor 1 (CD35) delivered by retrovirally infected syngeneic cells or by naked DNA injection prevents the progression of collagen-induced arthritis

Dreja¹,

Annenkov

Chernajovsky

2000

Arthritis & Rheumatism

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“…The anti-CD25 mAb PC61.5.3 [46], anti-IL-10 mAb JES5-2A5 [47], anti-IFN-g mAb R4-6A2 [48] and anti-TGF-b mAb HB 9849 [49] were isolated from hybridoma culture supernatants using cells purchased from the ATCC (Manassas, VA, USA) Allergen sensitization and challenge protocol OVA (1 mg/mL; Sigma, USA) in PBS was mixed with an equal volume of 10% aluminum potassium sulfate (alum; Sigma) in distilled water with shaking for 2 h at room temperature. After centrifugation at 750 Â g for 5 min, the OVA/alum complexes were resuspended into the distilled water with the original volume.…”

Section: Neutralizing Antibodiesmentioning

confidence: 99%

Protein/DNA vaccine‐induced antigen‐specific Treg confer protection against asthma

et al. 2008

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Asthma is a chronic inflammatory disorder caused by T-cell-mediated inflammation within airways. No antigen-specific treatment has been available. Using an OVA-induced murine asthma model, we find that co-immunization of an OVA epitope peptide with a DNA vaccine encoding the same epitope is able to prevent this experimental asthma as evidenced in the marked reduction of infiltrations of eosinophils and lymphocytes into the site of the allergen challenge. We demonstrate that the prevention of experimental asthma was directly related to the induction of a population of OVA-specific T-regulatory cells (Treg) exhibiting a CD4 1 CD25 À FoxP3 1 phenotype and expressing IL-10, TGF-b and IFN-c following the co-immunization. Blockade of IL-10 and TGF-b of the Treg by anti-IL-10 and TGF-b antibodies is partially able to reverse the suppression in vitro and in vivo, which caused the recurrence of the inflammation. Furthermore, adoptive transfer of the induced Treg is also able to suppress the OVA-induced asthma. To our knowledge, the combination of peptide with its cognate DNA vaccine protect experimental asthma via the induced epitope-specific Treg has not been previously reported and such strategy may lead to a novel immunotherapy against asthma in humans.Key words: Asthma Á Immune regulation Á Tolerance Á Treg cell Á Vaccination IntroductionAsthma is a chronic inflammatory disorder of the airways characterized by airway obstruction, increased airway responsiveness to a variety of stimuli as well as the infiltration by many inflammatory cells, including eosinophils, macrophages, lymphocytes and mast cells into lung tissue. CD4 1 T cells and Th2-biased cytokines (i.e. IL-4, IL-5 and IL-13) are believed to play a central role in the initiation and maintenance of the asthmatic response by regulating the production of IgE and the differentiation, recruitment and activation of mast cells and eosinophils [1][2][3].It has been proposed that Th1 cells, which secrete interferon-g (IFN-g), could protect against allergic disease by inhibiting the proliferation and development of Th2 cells [4] and IgE production [5]. Approaches of redirecting immunity from a Th2 type to Th1 type have also been demonstrated to result in temporary reduction of allergic reactions [6]. However, both autoimmune disease [7] and pathogen infection [8] induced Th1-biased immune responses were found to reduce the likelihood of allergy disease. Hansen et al. demonstrated that antigen-specific Th1 cells were ineffective in reducing the airway hyper-reactivity induced by Th2 cells but caused serious airway inflammation [9]. Thus, immunotherapeutic approaches using Th1 cell responses against asthma are rather complicated.Besides redirecting immunity-based approaches, several other strategies have also been considered to reduce allergic responses, including non-specific immunosuppressive drugs or monoclonal [21,22]. In this report, we further demonstrated that co-immunization of DNA and peptide vaccines against the same epitope-sequence of ovalbumin (OVA, aa 323...

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“…25 Subtypes of IFNs were determined by combinational uses of neutralizing monoclonal rat antibodies against mouse IFN-a (4E-A1), 26 IFN-b (7F-D3), 26 and IFN-g (R4-6A2) 27 in a bioassay.…”

Section: Ifn Bioassaymentioning

confidence: 99%

Therapeutic effect of intravenous delivery of lipoplexes containing the interferon-β gene and poly I: poly C in a murine lung metastasis model

et al. 2003

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We have evaluated and compared the efficacy of systemic administration of lipoplex formulations containing plasmids encoding IFN-b or IFN-g, and a synthetic double-strand RNA poly I:poly C (pI:pC), a type I IFN inducer, in a lung metastasis model in which colon carcinoma CT-26 cells were inoculated intravenously into immunocompatible mice. Injection of lipoplexes containing plasmid DNA, regardless of IFN gene insertion, stimulated a transient increase in the serum concentration of proinflammatory cytokines such as tumor necrosis factor (TNF)-a and IFN-g, while injection of lipoplexes containing pI:pC led to a low level of TNF-a and undetectable IFN-g production. Furthermore, injection of these lipoplexes containing plasmids resulted in the production of a mixture of type I and type II IFNs, partly derived from the inserted IFN genes, in lung tissue cultures. In tumor-prophylactic experiments, intravenous injection of lipoplexes containing plasmid, regardless of IFN gene insertion, showed a significant reduction in lung metastatic nodules probably due to proinflammatory cytokines such as TNF-a and IFN-g nonspecifically induced by the CpG motifs in the plasmid and the type I IFNs produced. On the other hand, the antimetastatic effect of pI:pC-lipoplex seemed to be due mainly to IFN-b induced by pI:pC. In established lung metastasis experiments, a single intravenous administration of lipoplexes containing IFN-b gene or pI:pC, but not other lipoplexes, showed a significant therapeutic effect on the tumor metastasis: reduction in tumor nodules and prolongation of survival time of tumor-burden mice. The therapeutic effects were specifically impaired by anti-IFN-b antibody treatment, indicating that IFN-b produced by the lipoplexes played an important role in the suppression of established metastatic lung tumors. Thus, the local IFN-b in the lung delivered by intravenous administration of lipoplex containing IFN-b gene or pI:pC may be a convenient and useful method of inhibiting established metastatic lung tumors.

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Monoclonal antibody to murine gamma interferon inhibits lymphokine-induced antiviral and macrophage tumoricidal activities.

Cited by 345 publications

References 12 publications

Soluble complement receptor 1 (CD35) delivered by retrovirally infected syngeneic cells or by naked DNA injection prevents the progression of collagen-induced arthritis

Soluble complement receptor 1 (CD35) delivered by retrovirally infected syngeneic cells or by naked DNA injection prevents the progression of collagen-induced arthritis

Protein/DNA vaccine‐induced antigen‐specific Treg confer protection against asthma

Therapeutic effect of intravenous delivery of lipoplexes containing the interferon-β gene and poly I: poly C in a murine lung metastasis model

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