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. 1983 Jun;80(11):3494–3498. doi: 10.1073/pnas.80.11.3494

Transferrin receptor induction in mitogen-stimulated human T lymphocytes is required for DNA synthesis and cell division and is regulated by interleukin 2.

L M Neckers, J Cossman
PMCID: PMC394071  PMID: 6304712

Abstract

Transferrin is required by many cells for growth. Mitogen-induced T lymphocyte proliferation is dependent on the presence of both interleukin 2 (IL-2; T-cell growth factor) and transferrin, even though resting lymphocytes do not have receptors for either. Exposure to mitogen (phytohemagglutinin) alone is sufficient to induce transient appearance of IL-2 receptors on lymphocytes. Using monoclonal antibodies to the IL-2 receptor and to the transferrin receptor, we examined those signals required for transferrin receptor induction during T lymphocyte proliferation. Our study has revealed that (i) monocytes, or a monocyte substitute such as the phorbol ester tetradecanoylphorbol 13-acetate, are required for transferrin receptor expression after mitogen exposure; (ii) the presence of IL-2 receptors is necessary for transferrin receptor induction; (iii) antibody to the IL-2 receptor inhibits thymidine incorporation (DNA synthesis) in lymphocytes, but only if administered before transferrin receptors have appeared; and (iv) antitransferrin receptor antibody inhibits DNA synthesis but has minimal effect on IL-2 receptor expression. Thus, IL-2 receptor induction leads to transferrin receptor induction and subsequent initiation of DNA synthesis. These data indicate that IL-2 stimulates T lymphocyte proliferation, at least in part, by induction of transferrin receptors on these cells.

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Selected References

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  1. Barnes D., Sato G. Serum-free cell culture: a unifying approach. Cell. 1980 Dec;22(3):649–655. doi: 10.1016/0092-8674(80)90540-1. [DOI] [PubMed] [Google Scholar]
  2. Braylan R. C., Benson N. A., Nourse V., Kruth H. S. Correlated analysis of cellular DNA, membrane antigens and light scatter of human lymphoid cells. Cytometry. 1982 Mar;2(5):337–343. doi: 10.1002/cyto.990020511. [DOI] [PubMed] [Google Scholar]
  3. Dillner-Centerlind M. L., Hammarström S., Perlmann P. Transferrin can replace serum for in vitro growth of mitogen-stimulated T lymphocytes. Eur J Immunol. 1979 Dec;9(12):942–948. doi: 10.1002/eji.1830091207. [DOI] [PubMed] [Google Scholar]
  4. Evans R. L., Faldetta T. J., Humphreys R. E., Pratt D. M., Yunis E. J., Schlossman S. F. Peripheral human T cells sensitized in mixed leukocyte culture synthesize and express Ia-like antigens. J Exp Med. 1978 Nov 1;148(5):1440–1445. doi: 10.1084/jem.148.5.1440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Goding J. W., Burns G. F. Monoclonal antibody OKT-9 recognizes the receptor for transferrin on human acute lymphocytic leukemia cells. J Immunol. 1981 Sep;127(3):1256–1258. [PubMed] [Google Scholar]
  6. Imrie R. C., Mueller G. C. Release of a lymphocyte growth promoter in leucocyte cultures. Nature. 1968 Sep 21;219(5160):1277–1279. doi: 10.1038/2191277a0. [DOI] [PubMed] [Google Scholar]
  7. Ko H. S., Fu S. M., Winchester R. J., Yu D. T., Kunkel H. G. Ia determinants on stimulated human T lymphocytes. Occurrence on mitogen- and antigen-activated T cells. J Exp Med. 1979 Aug 1;150(2):246–255. doi: 10.1084/jem.150.2.246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Koretzky G. A., Daniele R. P., Nowell P. C. A phorbol ester (TPA) can replace macrophages in human lymphocyte cultures stimulated with a mitogen but not with an antigen. J Immunol. 1982 Apr;128(4):1776–1780. [PubMed] [Google Scholar]
  9. Larrick J. W., Cresswell P. Modulation of cell surface iron transferrin receptors by cellular density and state of activation. J Supramol Struct. 1979;11(4):579–586. doi: 10.1002/jss.400110415. [DOI] [PubMed] [Google Scholar]
  10. Leonard W. J., Depper J. M., Uchiyama T., Smith K. A., Waldmann T. A., Greene W. C. 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):267–269. doi: 10.1038/300267a0. [DOI] [PubMed] [Google Scholar]
  11. Lotze M. T., Strausser J. L., Rosenberg S. A. In vitro growth of cytotoxic human lymphocytes. II. Use of T cell growth factor (TCGF) to clone human T cells. J Immunol. 1980 Jun;124(6):2972–2978. [PubMed] [Google Scholar]
  12. Maizel A. L., Mehta S. R., Hauft S., Franzini D., Lachman L. B., Ford R. J. Human T lymphocyte/monocyte interaction in response to lectin: kinetics of entry into the S-phase. J Immunol. 1981 Sep;127(3):1058–1064. [PubMed] [Google Scholar]
  13. Mier J. W., Gallo R. C. Purification and some characteristics of human T-cell growth factor from phytohemagglutinin-stimulated lymphocyte-conditioned media. Proc Natl Acad Sci U S A. 1980 Oct;77(10):6134–6138. doi: 10.1073/pnas.77.10.6134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Morgan D. A., Ruscetti F. W., Gallo R. Selective in vitro growth of T lymphocytes from normal human bone marrows. Science. 1976 Sep 10;193(4257):1007–1008. doi: 10.1126/science.181845. [DOI] [PubMed] [Google Scholar]
  15. Robb R. J., Munck A., Smith K. A. T cell growth factor receptors. Quantitation, specificity, and biological relevance. J Exp Med. 1981 Nov 1;154(5):1455–1474. doi: 10.1084/jem.154.5.1455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ruscetti F. W., Morgan D. A., Gallo R. C. Functional and morphologic characterization of human T cells continuously grown in vitro. J Immunol. 1977 Jul;119(1):131–138. [PubMed] [Google Scholar]
  17. Sutherland R., Delia D., Schneider C., Newman R., Kemshead J., Greaves M. Ubiquitous cell-surface glycoprotein on tumor cells is proliferation-associated receptor for transferrin. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4515–4519. doi: 10.1073/pnas.78.7.4515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Tormey D. C., Imrie R. C., Mueller G. C. Identification of transferrin as a lymphocyte growth promoter in human serum. Exp Cell Res. 1972 Sep;74(1):163–169. doi: 10.1016/0014-4827(72)90492-2. [DOI] [PubMed] [Google Scholar]
  19. Trowbridge I. S., Lopez F. Monoclonal antibody to transferrin receptor blocks transferrin binding and inhibits human tumor cell growth in vitro. Proc Natl Acad Sci U S A. 1982 Feb;79(4):1175–1179. doi: 10.1073/pnas.79.4.1175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Tsudo M., Uchiyama T., Takatsuki K., Uchino H., Yodoi J. Modulation of Tac antigen on activated human T cells by anti-Tac monoclonal antibody. J Immunol. 1982 Aug;129(2):592–595. [PubMed] [Google Scholar]
  21. Uchiyama T., Broder S., Waldmann T. A. 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):1393–1397. [PubMed] [Google Scholar]
  22. Uchiyama T., Nelson D. L., Fleisher T. A., Waldmann T. A. A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. II. Expression of Tac antigen on activated cytotoxic killer T cells, suppressor cells, and on one of two types of helper T cells. J Immunol. 1981 Apr;126(4):1398–1403. [PubMed] [Google Scholar]

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