Interleukin 2 Receptor Gene Expression in Normal Human T Lymphocytes

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 82; no. 18; pp. 6281 - 6285
• Main Authors: Leonard, Warren J., Kronke, Martin, Peffer, Nancy J., Depper, Joel M., Greene, Warner C.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.09.1985; National Acad Sciences
• Subjects: Biological and medical sciences; Blood; Cell Division; Cell Nucleus - metabolism; Cell surface receptors; Complementary DNA; DNA - genetics; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation; Genes; HLA Antigens - genetics; HLA-B7 Antigen; Humans; Interleukin-2; Lymphocyte Activation; Lymphocytes; Messenger RNA; Molecular and cellular biology; Molecular genetics; Poly A - genetics; Receptors; Receptors, Immunologic - genetics; Receptors, Interleukin-2; RNA; RNA, Messenger - genetics; T lymphocytes; T-Lymphocytes - physiology; Time Factors; Transcription, Genetic; Human; Regulation(control); Interleukin 2; Transcription; T-Lymphocyte; Lymphokine; Gene expression; Biological receptor
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.82.18.6281

We have used cDNAs for the human interleukin 2 (IL-2) receptor to study IL-2 receptor gene expression in normal activated T cells. Resting T cells do not contain detectable IL-2 receptor mRNA. Within 1 hr after stimulation with phytohemagglutinin (PHA), a large, presumably nuclear precursor RNA species is seen, which then gradually disappears. Mature IL-2 receptor mRNA forms appear within 8 hr after stimulation, reach peak levels between 8 and 24 hr, and then decline. Thus, in PHA-activated lymphocytes the rise and fall in IL-2 receptor mRNA levels precede by more than 24 hr the peak and decline of IL-2 receptor protein expression occurring at the cell surface. 4β -Phorbol 12-myristate 13-acetate (PMA) also stimulates IL-2 receptor mRNA and protein expression by T cells. Combinations of optimal concentrations of PHA and PMA produce an additive effect on IL-2 receptor mRNA levels, suggesting that PHA and PMA may induce IL-2 receptor gene expression through different, complementary mechanisms. Nuclease S1-protection assays indicate that IL-2 receptor mRNAs may differ in length due to the use of three different polyadenylylation signals. Further, these assays demonstrate the presence of transcripts that lack a 216-base segment within the protein-coding region and thus do not encode a functional IL-2 receptor. Nuclear transcription assays indicate that the increase in IL-2 receptor mRNA is reflected at the level of transcription. Thus, IL-2 receptor gene regulation controls IL-2 receptor expression at the cell surface and is intimately linked to the control of T-cell proliferation.