Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. 1988 Apr; 81(4): 1096–1102.
PMCID: PMC329636

Decreased proliferation, interleukin 2 synthesis, and interleukin 2 receptor expression are accompanied by decreased mRNA expression in phytohemagglutinin-stimulated cells from elderly donors.


Using cDNA probes to human interleukin 2 (IL2) and interleukin 2 receptor (IL2R), the amount of IL2 and IL2R mRNA produced by PHA stimulated peripheral blood mononuclear cells from young (less than 40 yr) and old (greater than 60 yr) donors was quantitated. Stimulated cell cultures from each individual were also examined for proliferative ability, expression of membrane IL2R, membrane IL2R density, and for the amount of IL2R shed into the culture supernatant. Induction of IL2 and IL2R mRNAs were decreased in cells from elderly individuals, as were the levels of IL2 secretion, the percentage of IL2R+ T cells and the density of membrane IL2R per cell. The results suggest that decreased expression of both IL2 and IL2R mRNA contributes to the low synthesis of IL2 and membrane IL2R, respectively, and is partially responsible for the diminished proliferative activity observed in lymphocytes from the elderly.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.4M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Smith KA. Interleukin 2. Annu Rev Immunol. 1984;2:319–333. [PubMed]
  • Meuer SC, Hussey RE, Cantrell DA, Hodgdon JC, Schlossman SF, Smith KA, Reinherz EL. Triggering of the T3-Ti antigen-receptor complex results in clonal T-cell proliferation through an interleukin 2-dependent autocrine pathway. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1509–1513. [PMC free article] [PubMed]
  • Cantrell DA, Smith KA. The interleukin-2 T-cell system: a new cell growth model. Science. 1984 Jun 22;224(4655):1312–1316. [PubMed]
  • Rubin LA, Kurman CC, Fritz ME, Biddison WE, Boutin B, Yarchoan R, Nelson DL. Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro. J Immunol. 1985 Nov;135(5):3172–3177. [PubMed]
  • Diamantstein T, Osawa H, Mouzaki A, Josimovic-Alasevic O. Regulation of interleukin-2 receptor expression and receptor release. Mol Immunol. 1986 Nov;23(11):1165–1172. [PubMed]
  • Rubin LA, Jay G, Nelson DL. The released interleukin 2 receptor binds interleukin 2 efficiently. J Immunol. 1986 Dec 15;137(12):3841–3844. [PubMed]
  • Thoman ML, Weigle WO. Reconstitution of in vivo cell-mediated lympholysis responses in aged mice with interleukin 2. J Immunol. 1985 Feb;134(2):949–952. [PubMed]
  • Gillis S, Kozak R, Durante M, Weksler ME. Immunological studies of aging. Decreased production of and response to T cell growth factor by lymphocytes from aged humans. J Clin Invest. 1981 Apr;67(4):937–942. [PMC free article] [PubMed]
  • Gilman SC, Rosenberg JS, Feldman JD. T lymphocytes of young and aged rats. II. Functional defects and the role of interleukin-2. J Immunol. 1982 Feb;128(2):644–650. [PubMed]
  • Rabinowich H, Goses Y, Reshef T, Klajman A. Interleukin-2 production and activity in aged humans. Mech Ageing Dev. 1985 Nov;32(2-3):213–226. [PubMed]
  • Arya SK, Wong-Staal F, Gallo RC. Dexamethasone-mediated inhibition of human T cell growth factor and gamma-interferon messenger RNA. J Immunol. 1984 Jul;133(1):273–276. [PubMed]
  • Krönke M, Leonard WJ, Depper JM, Greene WC. Sequential expression of genes involved in human T lymphocyte growth and differentiation. J Exp Med. 1985 Jun 1;161(6):1593–1598. [PMC free article] [PubMed]
  • Nagel JE, Chrest FJ, Adler WH. Mitogenic activity of 12-O-tetradecanoyl phorbol-13-acetate on peripheral blood lymphocytes from young and aged adults. Clin Exp Immunol. 1982 Jul;49(1):217–224. [PMC free article] [PubMed]
  • Gillis S, Ferm MM, Ou W, Smith KA. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed]
  • Nagel JE, Chrest FJ, Adler WH. Enumeration of T lymphocyte subsets by monoclonal antibodies in young and aged humans. J Immunol. 1981 Nov;127(5):2086–2088. [PubMed]
  • Nagel JE, Chrest FJ, Pyle RS, Adler WH. Monoclonal antibody analysis of T-lymphocyte subsets in young and aged adults. Immunol Commun. 1983;12(2):223–237. [PubMed]
  • Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. [PubMed]
  • Thomas PS. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. [PMC free article] [PubMed]
  • Leonard WJ, Depper JM, Crabtree GR, Rudikoff S, Pumphrey J, Robb RJ, Krönke M, Svetlik PB, Peffer NJ, Waldmann TA, et al. Molecular cloning and expression of cDNAs for the human interleukin-2 receptor. Nature. 1984 Oct 18;311(5987):626–631. [PubMed]
  • Holbrook NJ, Smith KA, Fornace AJ, Jr, Comeau CM, Wiskocil RL, Crabtree GR. T-cell growth factor: complete nucleotide sequence and organization of the gene in normal and malignant cells. Proc Natl Acad Sci U S A. 1984 Mar;81(6):1634–1638. [PMC free article] [PubMed]
  • Gunning P, Ponte P, Okayama H, Engel J, Blau H, Kedes L. Isolation and characterization of full-length cDNA clones for human alpha-, beta-, and gamma-actin mRNAs: skeletal but not cytoplasmic actins have an amino-terminal cysteine that is subsequently removed. Mol Cell Biol. 1983 May;3(5):787–795. [PMC free article] [PubMed]
  • Feinberg AP, Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. [PubMed]
  • Cantrell DA, Smith KA. Transient expression of interleukin 2 receptors. Consequences for T cell growth. J Exp Med. 1983 Dec 1;158(6):1895–1911. [PMC free article] [PubMed]
  • Kern JA, Reed JC, Daniele RP, Nowell PC. The role of the accessory cell in mitogen-stimulated human T cell gene expression. J Immunol. 1986 Aug 1;137(3):764–769. [PubMed]
  • Staiano-Coico L, Darzynkiewicz Z, Melamed MR, Weksler ME. Immunological studies of aging. IX. Impaired proliferation of T lymphocytes detected in elderly humans by flow cytometry. J Immunol. 1984 Apr;132(4):1788–1792. [PubMed]
  • Gutowski JK, Innes J, Weksler ME, Cohen S. Induction of DNA synthesis in isolated nuclei by cytoplasmic factors. II. Normal generation of cytoplasmic stimulatory factors by lymphocytes from aged humans with depressed proliferative responses. J Immunol. 1984 Feb;132(2):559–562. [PubMed]
  • Hegner D. Age-dependence of molecular and functional changes in biological membrane properties. Mech Ageing Dev. 1980 Sep-Oct;14(1-2):101–118. [PubMed]
  • Traill KN, Ratheiser K, Dietrich H, Sailer S, Zevenbergen JL, Wick G. Lack of correlation between serum cholesterol levels, lymphocyte plasma membrane fluidity and mitogen responsiveness in young and aged chickens. Mech Ageing Dev. 1984 Nov;28(1):123–138. [PubMed]
  • Thoman ML, Weigle WO. Cell-mediated immunity in aged mice: an underlying lesion in IL 2 synthesis. J Immunol. 1982 May;128(5):2358–2361. [PubMed]
  • Wu WT, Pahlavani M, Cheung HT, Richardson A. The effect of aging on the expression of interleukin 2 messenger ribonucleic acid. Cell Immunol. 1986 Jun;100(1):224–231. [PubMed]
  • Smith KA, Cantrell DA. Interleukin 2 regulates its own receptors. Proc Natl Acad Sci U S A. 1985 Feb;82(3):864–868. [PMC free article] [PubMed]
  • Robb RJ, Rusk CM, Yodoi J, Greene WC. Interleukin 2 binding molecule distinct from the Tac protein: analysis of its role in formation of high-affinity receptors. Proc Natl Acad Sci U S A. 1987 Apr;84(7):2002–2006. [PMC free article] [PubMed]
  • Dukovich M, Wano Y, Le thi Bich Thuy, Katz P, Cullen BR, Kehrl JH, Greene WC. A second human interleukin-2 binding protein that may be a component of high-affinity interleukin-2 receptors. Nature. 1987 Jun 11;327(6122):518–522. [PubMed]
  • Greene WC. The human interleukin-2 receptor: a molecular and biochemical analysis of structure and function. Clin Res. 1987 Sep;35(5):439–450. [PubMed]
  • Sharon M, Klausner RD, Cullen BR, Chizzonite R, Leonard WJ. Novel interleukin-2 receptor subunit detected by cross-linking under high-affinity conditions. Science. 1986 Nov 14;234(4778):859–863. [PubMed]
  • Tsudo M, Kozak RW, Goldman CK, Waldmann TA. Demonstration of a non-Tac peptide that binds interleukin 2: a potential participant in a multichain interleukin 2 receptor complex. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9694–9698. [PMC free article] [PubMed]
  • Teshigawara K, Wang HM, Kato K, Smith KA. Interleukin 2 high-affinity receptor expression requires two distinct binding proteins. J Exp Med. 1987 Jan 1;165(1):223–238. [PMC free article] [PubMed]
  • Robb RJ, Greene WC. Internalization of interleukin 2 is mediated by the beta chain of the high-affinity interleukin 2 receptor. J Exp Med. 1987 Apr 1;165(4):1201–1206. [PMC free article] [PubMed]
  • Siegel JP, Sharon M, Smith PL, Leonard WJ. The IL-2 receptor beta chain (p70): role in mediating signals for LAK, NK, and proliferative activities. Science. 1987 Oct 2;238(4823):75–78. [PubMed]
  • Tsudo M, Goldman CK, Bongiovanni KF, Chan WC, Winton EF, Yagita M, Grimm EA, Waldmann TA. The p75 peptide is the receptor for interleukin 2 expressed on large granular lymphocytes and is responsible for the interleukin 2 activation of these cells. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5394–5398. [PMC free article] [PubMed]
  • Bich-Thuy LT, Dukovich M, Peffer NJ, Fauci AS, Kehrl JH, Greene WC. Direct activation of human resting T cells by IL 2: the role of an IL 2 receptor distinct from the Tac protein. J Immunol. 1987 Sep 1;139(5):1550–1556. [PubMed]
  • Kumar A, Moreau JL, Baran D, Thèze J. Evidence for negative regulation of T cell growth by low affinity interleukin 2 receptors. J Immunol. 1987 Mar 1;138(5):1485–1493. [PubMed]
  • Jacques Y, Le Mauff B, Boeffard F, Godard A, Soulillou JP. A soluble interleukin 2 receptor produced by a normal alloreactive human T cell clone binds interleukin 2 with low affinity. J Immunol. 1987 Oct 1;139(7):2308–2316. [PubMed]
  • Vie H, Miller RA. Decline, with age, in the proportion of mouse T cells that express IL-2 receptors after mitogen stimulation. Mech Ageing Dev. 1986 Feb;33(3):313–322. [PubMed]
  • Grabstein K, Dower S, Gillis S, Urdal D, Larsen A. Expression of interleukin 2, interferon-gamma, and the IL 2 receptor by human peripheral blood lymphocytes. J Immunol. 1986 Jun 15;136(12):4503–4508. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    NCBI Bookshelf books that cite the current articles.
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...