Interleukin 2 (IL-2) Augments Transcription of the IL-2 Receptor Gene

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1985 Jun 1

PMID 2987968

Citations 103

Authors

J M Depper

W J Leonard

C Drogula

M Kronke

T A Waldmann

W C Greene

Affiliations

Soon will be listed here.

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.

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References

Pledger W, Stiles C, Antoniades H, Scher C . 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; 74(10):4481-5. PMC: 431967. DOI: 10.1073/pnas.74.10.4481. View

Welte K, Andreeff M, PLATZER E, Holloway K, Rubin B, Moore M . Interleukin 2 regulates the expression of Tac antigen on peripheral blood T lymphocytes. J Exp Med. 1984; 160(5):1390-403. PMC: 2187497. DOI: 10.1084/jem.160.5.1390. View

Chirgwin J, Przybyla A, MacDonald R, Rutter W . Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979; 18(24):5294-9. DOI: 10.1021/bi00591a005. View

Yodoi J, Ishizaka K . Induction of Fc epsilon-receptor bearing cells in vitro in human peripheral lymphocytes. J Immunol. 1980; 124(2):934-8. View

Smith K . T-cell growth factor. Immunol Rev. 1980; 51:337-57. DOI: 10.1111/j.1600-065x.1980.tb00327.x. View

Uchiyama T, Broder S, Waldmann T . 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; 126(4):1393-7. View

Hoover R, Dieckgraefe B, Lynch R . T cells with Fc receptors for IgA: induction of T alpha cells in vivo and in vitro by purified IgA. J Immunol. 1981; 127(4):1560-3. View

Robb R, Munck A, Smith K . T cell growth factor receptors. Quantitation, specificity, and biological relevance. J Exp Med. 1981; 154(5):1455-74. PMC: 2186509. DOI: 10.1084/jem.154.5.1455. View

Leonard W, Depper J, Uchiyama T, Smith K, Waldmann T, Greene W . A monoclonal antibody that appears to recognize the receptor for human T-cell growth factor; partial characterization of the receptor. Nature. 1982; 300(5889):267-9. DOI: 10.1038/300267a0. View

10.

Stevens R, Austen K, NISSLEY S . Insulin-induced increase in insulin binding to cultured chondrosarcoma chondrocytes. J Biol Chem. 1983; 258(5):2940-4. View

11.

Neckers L, Cossman J . 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; 80(11):3494-8. PMC: 394071. DOI: 10.1073/pnas.80.11.3494. View

12.

Feinberg A, Vogelstein B . A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983; 132(1):6-13. DOI: 10.1016/0003-2697(83)90418-9. View

13.

Cantrell D, Smith K . Transient expression of interleukin 2 receptors. Consequences for T cell growth. J Exp Med. 1983; 158(6):1895-911. PMC: 2187178. DOI: 10.1084/jem.158.6.1895. View

14.

Kelly K, Cochran B, Stiles C, Leder P . Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell. 1983; 35(3 Pt 2):603-10. DOI: 10.1016/0092-8674(83)90092-2. View

15.

Hemler M, Brenner M, McLEAN J, Strominger J . Antigenic stimulation regulates the level of expression of interleukin 2 receptor on human T cells. Proc Natl Acad Sci U S A. 1984; 81(7):2172-5. PMC: 345459. DOI: 10.1073/pnas.81.7.2172. View

16.

Wang A, Lu S, Mark D . Site-specific mutagenesis of the human interleukin-2 gene: structure-function analysis of the cysteine residues. Science. 1984; 224(4656):1431-3. DOI: 10.1126/science.6427925. View

17.

Reem G, Yeh N . Interleukin 2 regulates expression of its receptor and synthesis of gamma interferon by human T lymphocytes. Science. 1984; 225(4660):429-30. DOI: 10.1126/science.6429853. View

18.

Depper J, Leonard W, Kronke M, Waldmann T, Greene W . Augmented T cell growth factor receptor expression in HTLV-1-infected human leukemic T cells. J Immunol. 1984; 133(4):1691-5. View

19.

Kronke M, Leonard W, Depper J, Arya S, Wong-Staal F, Gallo R . Cyclosporin A inhibits T-cell growth factor gene expression at the level of mRNA transcription. Proc Natl Acad Sci U S A. 1984; 81(16):5214-8. PMC: 391668. DOI: 10.1073/pnas.81.16.5214. View

20.

Robb R, Greene W, Rusk C . Low and high affinity cellular receptors for interleukin 2. Implications for the level of Tac antigen. J Exp Med. 1984; 160(4):1126-46. PMC: 2187485. DOI: 10.1084/jem.160.4.1126. View