Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells - PubMed (original) (raw)
. 1991 May 1;146(9):3074-81.
Affiliations
- PMID: 1673147
Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells
S F Wolf et al. J Immunol. 1991.
Abstract
Previously we have reported the purification and characterization of a novel cytokine from an EBV-transformed B cell line, RPMI 8866. This factor, termed natural killer cell stimulatory factor (NKSF), possessed pleiotropic activities including the induction of IFN-gamma from PBL, enhancement of cytotoxicity by NK cells, and stimulation of the proliferation of PBL. Purified NKSF was found to be a disulfide-linked heterodimeric protein composed of 35-kDa and 40-kDa subunits (p35 and p40). We now report the molecular cloning of cDNA for both subunits of NKSF from RPMI 8866 cellular RNA. The cDNA sequences indicate that both genes are novel, and Southern blot analysis confirmed that both cDNA are of human genomic origin. [35S]Methionine labeling indicated that cos-1 cells transfected with either p35 or p40 cDNA produced unique protein species of appropriate size. Methionine labeling of cos-1 cells cotransfected with p35 plus p40 cDNA yielded a broad band migrating between 70 and 90 kDa on a nonreducing gel. Reduction of this high molecular weight material yielded bands correlating with p35 and p40 gene products. Only culture supernatant from cotransfected cos-1 cells had a high level of NKSF biologic activity. That the high molecular weight material was responsible for this activity was indicated by the observation that biologic activity in the culture supernatant migrated at 70 to 90 kDa in a nonreducing gel. Furthermore, anti-p40 serum was able to block the biologic activities of both recombinant and natural NKSF, which indicates that it is a component of the active protein. In contrast, no activity could be detected in the supernatants of cos-1 cells transfected with p40 or p35 cDNA alone. The spectrum of biologic activity produced by cotransfected cos-1 cells was the same as NKSF purified to homogeneity from the RPMI 8866 cell line. A synergistic augmentation of some of these responses was found by the addition of IL-2 or the co-stimulators PHA or phorbol diester. The synergistic stimulation by NKSF plus IL-2 of T and NK function supports the possibility that these cytokines might prove useful in cancer therapy.
Similar articles
- Cloning and expression of murine IL-12.
Schoenhaut DS, Chua AO, Wolitzky AG, Quinn PM, Dwyer CM, McComas W, Familletti PC, Gately MK, Gubler U. Schoenhaut DS, et al. J Immunol. 1992 Jun 1;148(11):3433-40. J Immunol. 1992. PMID: 1350290 - Production of natural killer cell stimulatory factor (interleukin 12) by peripheral blood mononuclear cells.
D'Andrea A, Rengaraju M, Valiante NM, Chehimi J, Kubin M, Aste M, Chan SH, Kobayashi M, Young D, Nickbarg E, et al. D'Andrea A, et al. J Exp Med. 1992 Nov 1;176(5):1387-98. doi: 10.1084/jem.176.5.1387. J Exp Med. 1992. PMID: 1357073 Free PMC article. - Antitumor effects of interleukin-12 (IL-12): applications for the immunotherapy and gene therapy of cancer.
Tahara H, Lotze MT. Tahara H, et al. Gene Ther. 1995 Mar;2(2):96-106. Gene Ther. 1995. PMID: 7719935 Review. - [Function and molecular structure of IL-12].
Oshimi K, Hoshino S. Oshimi K, et al. Nihon Rinsho. 1992 Aug;50(8):1840-4. Nihon Rinsho. 1992. PMID: 1359171 Review. Japanese.
Cited by
- Ebi3 Binding to IFN-γ and IL-10 Limits Their Function.
Scott EN, Ye C, Yano H, Lipatova Z, Brunazzi E, Vignali KM, Workman CJ, Vignali DAA. Scott EN, et al. J Immunol. 2024 Oct 15;213(8):1115-1124. doi: 10.4049/jimmunol.2400236. J Immunol. 2024. PMID: 39240167 - The IL-12 family of cytokines: pathogenetic role in diabetic retinopathy and therapeutic approaches to correction.
Wang D, Liu R. Wang D, et al. Naunyn Schmiedebergs Arch Pharmacol. 2024 Aug 9. doi: 10.1007/s00210-024-03360-9. Online ahead of print. Naunyn Schmiedebergs Arch Pharmacol. 2024. PMID: 39120722 Review. - High production of IL-12 by human dendritic cells stimulated with combinations of pattern-recognition receptor agonists.
Gilmour BC, Corthay A, Øynebråten I. Gilmour BC, et al. NPJ Vaccines. 2024 May 3;9(1):83. doi: 10.1038/s41541-024-00869-1. NPJ Vaccines. 2024. PMID: 38702320 Free PMC article. - Structures of complete extracellular receptor assemblies mediated by IL-12 and IL-23.
Bloch Y, Felix J, Merceron R, Provost M, Symakani RA, De Backer R, Lambert E, Mehdipour AR, Savvides SN. Bloch Y, et al. Nat Struct Mol Biol. 2024 Apr;31(4):591-597. doi: 10.1038/s41594-023-01190-6. Epub 2024 Jan 29. Nat Struct Mol Biol. 2024. PMID: 38287195 - Modulation of Suppressive Activity and Proliferation of Human Regulatory T Cells by Splice-Switching Oligonucleotides Targeting FoxP3 Pre-mRNA.
Blinova VG, Gladilina YA, Abramova AA, Eliseeva DD, Vtorushina VV, Shishparenok AN, Zhdanov DD. Blinova VG, et al. Cells. 2023 Dec 29;13(1):77. doi: 10.3390/cells13010077. Cells. 2023. PMID: 38201281 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Other Literature Sources
Molecular Biology Databases
Research Materials