Partial characterization of gamma (immune) interferon mRNA extracted from human lymphocytes.

Taniguchi, Tadatsugu; Pang, Roy H. L.; Yip, Y. K.; Henriksen, Dorothy; Vilček, Ján

doi:10.1073/pnas.78.6.3469

Cited by 33 publications

(2 citation statements)

References 23 publications

(28 reference statements)

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“…Human chromosomal DNA was extracted as described (9) from the peripheral blood lymphocytes of healthy donors (10) or from Jurkat-lll cells (6). Blotting analysis of the total DNA was carried out according to the procedure of Southern (11).…”

Section: Methodsmentioning

confidence: 99%

Structure of the human interleukin 2 gene.

Fujita¹,

Takaoka²,

Matsui³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

177

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We have cloned two species of EcoRI-cleaved DNA segments that together cover the entire sequence for the human interleukin 2 gene and have determined the nucleotide sequence of the gene and its flanking regions. The gene contains three introns and the exon sequences can be aligned with the previously reported cDNA sequence almost perfectly except for a few nucleotides in the 3' nontranslated region. The promoter region contains a prototype "TATA" sequence as well as a notable palindromic sequence. Particularly interesting is the presence of sequences in this region that are homologous to the promoter region of the human interferon-y gene. In addition, a sequence that closely resembles the core sequence for the viral enhancer elements has been found in the second intron. Such sequences may play a role in the expression of the interleukin 2 gene in lectin-or antigen-stimulated T lymphocytes.Interleukin 2 (IL-2) is a lymphokine produced by lectin-or antigen-activated T cells (1, 2). Among the various biological activities ascribed to IL-2 (1, 3-5), the principal role of this immunoregulatory molecule appears to be the stimulation of the proliferative response of activated T-cell clones and hence it plays a key role in the regulation of the T-cell clonal expansion (5).We recently reported the isolation and nucleotide sequence of a cloned cDNA for human IL-2 (6). The deduced amino acid sequence of mature IL-2 showed very little homology with any humoral factors whose structures have been elucidated. Although human IL-2 is reportedly heterogeneous (7), we have been able to identify only a single species of mRNA coding for IL-2 in both a leukemia T-cell line (Jurkat-lll) and normal peripheral blood lymphocytes (ref. 6; unpublished results).Despite extensive studies on the biological characteristics of IL-2, little is known about the regulation of IL-2 expression. It is well documented that the production of IL-2 is specific for mature thymus-derived T cells whereas IL-2-responsive cells belong to a distinct subset (5). Since neither IL-2 activity nor IL-2-specific mRNA is produced by such producer cells without induction by lectins or antigens (1, 6, 8), IL-2 expression is likely to be controlled at the mRNA transcription level.To study the structural organization and to obtain further information about the expression of the human IL-2 gene, we have cloned and analyzed the IL-2 chromosomal gene and its flanking regions. MATERIALS AND METHODSPreparation and Blotting Analysis of Human DNA. Human chromosomal DNA was extracted as described (9) from the peripheral blood lymphocytes of healthy donors (10) or from Jurkat-lll cells (6). Blotting analysis of the total DNA was carried out according to the procedure of Southern (11).Cloning and Sequence Analysis.of the IL-2 Gene. DNA (500 Ag) from peripheral blood lymphocytes was digested with EcoRI and fractionated on a 10-40% linear sucrose gradient in 20 mM Tris1HCl, pH 8.0/1 M NaCl/5 mM EDTA by centrifugation at 27,000 rpm for 24 hr at 4°C in a Beckman SW28 rotor. DN...

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Section: Methodsmentioning

confidence: 99%

Structure of the human interleukin 2 gene.

Fujita¹,

Takaoka²,

Matsui³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

177

View full text Add to dashboard Cite

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“…Only recently has extensive purification of IFN-t been achieved (22) and this has allowed a more precise determination of the molecular size (23). The mRNA for IFN-'T isolated from human peripheral blood lymphocyte (PBL) cultures has been partially enriched and translated in Xenopus laevis oocytes (24)(25)(26)(27).…”

Section: Introductionmentioning

confidence: 99%

Molecular cloning of human immune interferon cDNA and its expression in eukaryotic cells

Devos¹,

Cheroutre²,

Taya³

et al. 1982

Nucl Acids Res

183

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Starting with mRNA derived from Staphylococcal enterotoxin A induced human splenocytes, dsDNA was synthesized and inserted into unique BamHI site of the eukaryotic expression vector pSV529 (1). A recombinant plasmid containing human immune interferon (IFN-gamma) cDNA was identified by hybridization of plasmid inserted DNA bound onto nitrocellulose filters with mRNA derived from SEA-induced splenocytes, translation of the eluted RNA in Xenopus laevis oocytes and assaying for IFN activity. Plasmids containing the entire human IFN-gamma cDNA sequence were identified by colony hybridization and were sequenced. A unique coding region was identified which predicted a protein of 166 amino acids, the 20 N-terminal amino acids of which presumably represent a signal peptide. After transfection of monkey cells with plasmid DNA isolated from one of the recombinant clones (pHIIF-SV-gamma 1), IFN was excreted into the culture medium. This IFN was not distinguishable from human IFN-gamma by serological criteria or by cell target species specificity.

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Recombinant interferon beta and gamma in the treatment of adult T-cell leukemia

Tamura

Makino

Araki

et al. 1987

Cancer

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Adult T-cell leukemia (ATL) is one of the most difficult diseases to treat because of severe underlying immune deficiency and metabolic disturbance. Interferon has potent antiviral, antiproliferative, and immunomodulating properties, and therefore, this may be a good agent to treat such immune deficient patients with peripheral T-cell leukemia. During a period from April 1984 to August 1985, six patients were treated with interferon-beta (IFN-beta), and interferon-gamma (IFN-gamma) was given to five patients. Three patients achieved partial remission by IFN-beta administration with a response duration of 1, 1.5, and 12 months respectively, whereas one complete remission and two partial responses were experienced by IFN-gamma treatment with 4, 4, and 2 months of response. Side effects of IFN-beta were similar to those of IFN-gamma including fever, chills, fatigue, mild hematologic depression, and transient hepatic enzyme abnormalities. These promising results warrant further well-designed clinical trials including combination with other agents or modalities of treatment.

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Partial characterization of gamma (immune) interferon mRNA extracted from human lymphocytes.

Cited by 33 publications

References 23 publications

Structure of the human interleukin 2 gene.

Structure of the human interleukin 2 gene.

Molecular cloning of human immune interferon cDNA and its expression in eukaryotic cells

Recombinant interferon beta and gamma in the treatment of adult T-cell leukemia

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