Abstract
We demonstrate that purified interleukin 2 (IL-2) can directly upregulate IL-2 receptor expression on phytohemagglutinin-activated T lymphocytes maintained in culture until IL-2 receptor expression had markedly declined. The IL-2-induced increase in IL-2 receptor number is maximal within 12 hr, requires new RNA and protein synthesis, and is mediated by an interaction of ligand with the high-affinity receptors for IL-2. IL-2 stimulation results in increased accumulation of IL-2 receptor mRNA within 4 hr, while an increase in IL-2 receptor gene transcription is detected within 30 min in isolated nuclei. In addition, IL-2 incubation results in increased amounts of c-myc and transferrin receptor mRNA, but it does not augment levels of mRNA encoding the beta chain of the T-cell receptor for antigen. These results demonstrate that IL-2 can directly upregulate transcription and expression of its own receptor and, therefore, indicate that IL-2 may regulate IL-2-dependent immune responses, in part, by influencing the expression of IL-2 receptors.
MeSH Terms
Cells, Cultured
Gene Expression Regulation/drug effects
Humans
Interleukin-2/pharmacology
Lymphocytes/physiology
Oncogenes
Phytohemagglutinins/pharmacology
Protein Biosynthesis
RNA, Messenger/genetics
Receptors, Cell Surface/genetics
Receptors, Immunologic/genetics,metabolism
Receptors, Interleukin-2
Receptors, Transferrin
Tetradecanoylphorbol Acetate/pharmacology
Transcription, Genetic/drug effects
Chemicals
Interleukin-2
Phytohemagglutinins
RNA, Messenger
Receptors, Cell Surface
Receptors, Immunologic
Receptors, Interleukin-2
Receptors, Transferrin
Tetradecanoylphorbol Acetate
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Depper J M
Leonard W J
Drogula C
Krönke M
Waldmann T A
Greene W C
References (23)
23 references, click to expand
-
Induction of DNA synthesis in BALB/c 3T3 cells by serum components: reevaluation of the commitment process.
Proc Natl Acad Sci U S A. 1977 Oct;74(10):4481-5
PMID: 270695
-
Interleukin 2 regulates the expression of Tac antigen on peripheral blood T lymphocytes.
J Exp Med. 1984 Nov 1;160(5):1390-403
PMID: 6092510
-
Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.
Biochemistry. 1979 Nov 27;18(24):5294-9
PMID: 518835
-
Induction of Fc epsilon-receptor bearing cells in vitro in human peripheral lymphocytes.
J Immunol. 1980 Feb;124(2):934-8
PMID: 7356720
-
T-cell growth factor.
Immunol Rev. 1980;51:337-57
PMID: 7000676
-
A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. I. Production of anti-Tac monoclonal antibody and distribution of Tac (+) cells.
J Immunol. 1981 Apr;126(4):1393-7
PMID: 6970774
-
T cells with Fc receptors for IgA: induction of T alpha cells in vivo and in vitro by purified IgA.
J Immunol. 1981 Oct;127(4):1560-3
PMID: 6974197
-
T cell growth factor receptors. Quantitation, specificity, and biological relevance.
J Exp Med. 1981 Nov 1;154(5):1455-74
PMID: 6975347
-
A monoclonal antibody that appears to recognize the receptor for human T-cell growth factor; partial characterization of the receptor.
Nature. 1982 Nov 18;300(5889):267-9
PMID: 6815536
-
Insulin-induced increase in insulin binding to cultured chondrosarcoma chondrocytes.
J Biol Chem. 1983 Mar 10;258(5):2940-4
PMID: 6338008
-
Transferrin receptor induction in mitogen-stimulated human T lymphocytes is required for DNA synthesis and cell division and is regulated by interleukin 2.
Proc Natl Acad Sci U S A. 1983 Jun;80(11):3494-8
PMID: 6304712
-
A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity.
Anal Biochem. 1983 Jul 1;132(1):6-13
PMID: 6312838
-
Transient expression of interleukin 2 receptors. Consequences for T cell growth.
J Exp Med. 1983 Dec 1;158(6):1895-911
PMID: 6606011
-
Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor.
Cell. 1983 Dec;35(3 Pt 2):603-10
PMID: 6606489
-
Antigenic stimulation regulates the level of expression of interleukin 2 receptor on human T cells.
Proc Natl Acad Sci U S A. 1984 Apr;81(7):2172-5
PMID: 6425828
-
Site-specific mutagenesis of the human interleukin-2 gene: structure-function analysis of the cysteine residues.
Science. 1984 Jun 29;224(4656):1431-3
PMID: 6427925
-
Interleukin 2 regulates expression of its receptor and synthesis of gamma interferon by human T lymphocytes.
Science. 1984 Jul 27;225(4660):429-30
PMID: 6429853
-
Augmented T cell growth factor receptor expression in HTLV-1-infected human leukemic T cells.
J Immunol. 1984 Oct;133(4):1691-5
PMID: 6088625
-
Cyclosporin A inhibits T-cell growth factor gene expression at the level of mRNA transcription.
Proc Natl Acad Sci U S A. 1984 Aug;81(16):5214-8
PMID: 6332315
-
Low and high affinity cellular receptors for interleukin 2. Implications for the level of Tac antigen.
J Exp Med. 1984 Oct 1;160(4):1126-46
PMID: 6090574
-
Molecular cloning and expression of cDNAs for the human interleukin-2 receptor.
Nature. 1984 Oct 18-24;311(5987):626-31
PMID: 6090948
-
Regulation of interleukin 2 receptor expression: effects of phorbol diester, phospholipase C, and reexposure to lectin or antigen.
J Immunol. 1984 Dec;133(6):3054-61
PMID: 6092466
-
Transcriptional regulation of the ovalbumin and conalbumin genes by steroid hormones in chick oviduct.
J Biol Chem. 1979 Sep 25;254(18):9050-8
PMID: 479179