Human natural interferon-α producing cells

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Abstract

Interferons (IFNs) are critical components of the host immune system, serving as antiviral agents, immunomodulators and inhibitors of cell growth. Among peripheral blood mononuclear cells, the primary IFN-α-producing cell is a light density, HLA-DR ⁺ cell negative for cell surface markers typical for T cells, B cells, monocytes, natural-killer or progenitor cells and has been tentatively the ‘natural’ IFN-producing cell' or NIPC. Although present in very low frequency (approximately 1:1000 among peripheral blood mononuclear cells), the NIPC are very potent, with an individual cell able to produce 1–2 IU of IFN. In this review, the characteristics, phenotype, regulation and relationship of NIPC to human disease are discussed.

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Most cited references 112

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Systemic lupus erythematosus: presence in human serum of an unusual acid-labile leukocyte interferon.

J Klippel, Colin Black, O T Preble … (1982)

A previously undescribed species of human leukocyte, or alpha, interferon is present in the serum of many patients with systemic lupus erythematosus. It was shown to be alpha-interferon by neutralization with specific antiserums, affinity column chromatography, and antiviral activity on bovine cells. However, 23 of 30 interferon samples tested were inactivated by incubation at pH 2, a characteristic of human "immune," or gamma, interferon. Multiple samples of interferon from the same patient had similar biological properties, but samples from different patients were not all identical, suggesting that several variants of this species of human alpha-interferon may exist.

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Single amino acid changes in the viral glycoprotein M affect induction of alpha interferon by the coronavirus transmissible gastroenteritis virus.

J Gelfi, B Charley, L Lavenant … (1992)

Transmissible gastroenteritis virus, an enteropathogenic coronavirus of swine, is a potent inducer of alpha interferon (IFN-alpha) both in vitro and in vivo. Previous studies have shown that virus-infected fixed cells or viral suspensions were able to induce an early and strong IFN-alpha synthesis by naive lymphocytes. Two monoclonal antibodies directed against the viral membrane glycoprotein M (29,000; formerly E1) were found to markedly inhibit virus-induced IFN production, thus assigning to M protein a potential effector role in this phenomenon (B. Charley and H. Laude, J. Virol. 62:8-11, 1988). The present report describes the selection and characterization of a collection of 125 mutant viruses which escaped complement-mediated neutralization by two IFN induction-blocking anti-M protein monoclonal antibodies. Two of these mutants, designated H92 and dm49-4, were found to exhibit a markedly reduced interferogenic activity. IFN synthesis by lymphocytes incubated with purified suspensions of these mutants was 30- to 300-fold lower than that of the parental virus. The transcription of IFN-alpha genes following induction by each mutant was decreased proportionally, as evidenced by Northern (RNA) blot analysis. The sequence of the M gene of 20 complement-mediated neutralization-resistant mutants, including the 2 defective mutants, was determined by direct sequencing of genome RNA. Thirteen distinct amino acid changes were predicted, all located at positions 6 to 22 from the N terminus of the mature M protein and within the putative ectodomain of the molecule. Two substitutions, Thr-17 to Ile and Ser-19 to Pro, were assumed to generate the defective phenotypes of mutants dm49-4 and H92, respectively. The alteration of an Asn-Ser-Thr sequence in dm49-4 virus led to the synthesis of an M protein devoid of a glycan side chain, which suggests a possible involvement of this structure in IFN induction. Overall, these data supported the view that an interferogenic determinant resides in the N-terminal, exposed part of the molecule and provided further evidence for the direct role of M protein in the induction of IFN-alpha by transmissible gastroenteritis virus. The acronym VIP (viral interferogenic protein) is proposed as a designation for this particular class of proteins.

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Induction of alpha interferon by transmissible gastroenteritis coronavirus: role of transmembrane glycoprotein E1.

H Laude, B Charley (1987)

Epithelial cells infected with the coronavirus transmissible gastroenteritis virus (TGEV) and fixed by glutaraldehyde induced a high alpha interferon (IFN-alpha) production in nonimmune porcine as well as human or bovine peripheral blood mononuclear cells (PBMC). IFN-alpha was detected as early as 3 h after exposure of PBMC to infected cells and at producer/inducer cell ratios as low as 1/1. Two of four monoclonal antibodies directed against the viral transmembrane glycoprotein E1 could block the IFN-inducing capacity of both TGEV-infected cells and viral particles. On the other hand, IFN-alpha induction was not markedly affected by monoclonal antibodies directed against other E1 epitopes, against peplomer glycoprotein E2, or against nucleocapsid protein. Thus, these findings strongly imply that IFN induction by TGEV results from interactions between an outer membrane domain of E1 and the PBMC membrane.

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Journal

Journal ID (nlm-ta): Pharmacol Ther

Journal ID (iso-abbrev): Pharmacol. Ther

Title: Pharmacology & Therapeutics

Publisher: Published by Elsevier Inc.

ISSN (Print): 0163-7258

ISSN (Electronic): 1879-016X

Publication date PMC-release: 14 November 2002

Publication date (Print): 1993

Publication date (Electronic): 14 November 2002

Volume: 60

Issue: 1

Pages: 39-62

Affiliations

Department of Laboratory Medicine and Pathology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 So. Orange Avenue, Newark, NJ 07103, U.S.A.

Article

Publisher ID: 0163-7258(93)90021-5

DOI: 10.1016/0163-7258(93)90021-5

PMC ID: 7133642

PubMed ID: 8127923

SO-VID: 0ce0c426-3acf-468e-85ec-7defaf8a0377

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Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

Human natural interferon-α producing cells

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Most cited references 112

Systemic lupus erythematosus: presence in human serum of an unusual acid-labile leukocyte interferon.

Single amino acid changes in the viral glycoprotein M affect induction of alpha interferon by the coronavirus transmissible gastroenteritis virus.

Induction of alpha interferon by transmissible gastroenteritis coronavirus: role of transmembrane glycoprotein E1.

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