Abstract
The proliferation of T lymphocytes is regulated in part through their membrane receptors for antigen and for T cell growth factor (interleukin 2, IL-2). Stimulation of resting T cells by specific antigen or by mitogenic cells (phytohemagglutinin, concanavalin A) in the presence of accessory cells bearing surface antigens encoded by genes in the major histocompatibility complex (MHC) locus induces T cells to express receptors for IL-2 and (some but not all T cells) to secrete this growth factor. The interaction of IL-2 with its cellular receptor on antigen- or lectin-activated T cells subsequently results in expression of transferrin receptors. Binding of serum transferrin to its receptor in late G1 phase of the cell cycle is then required for T cells to undergo the G1 → S phase transition, thereby initiating DNA synthesis and resulting ultimately in cell division. Other growth factors, including insulin and insulin-like growth factors, do not appear necessary, at least for short-term growth of T cells (reviewed in 1–3).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
W. C. Greene, and R. J. Robb. Receptors for T cell growth factor: structure, function, and expression in normal and neoplastic cells. Contemp. Top Molecular Immun. 10:1, (1985).
D. A. Cantrell, and K. A. Smith. The interleukin 2 T-cell system: A new cell growth model. Science 224:1312, (1984).
L. M. Nickers, and J. Cossman. Transferrin receptor induction in mitogen-stimulated human T lymphocytes is required for DNA synthesis and cell division and is regulated by interleukin 2 (TCGF). In: Thymic Hormones and Lymphokines, ed. Goldstein, Plenum Press p 383, (1984).
J. M. Bishop. Viral oncogenes. Cell 42:23, (1985).
K. Kelly, B. H. Cochran, S. D. Stiles, and P. Leder. Cell-specific regulation of the c-myc gene by lymphocyte-mitogens and platelet-derived growth factor. Cell 35:603, (1983).
J. Milner, and S. Milner. SV40–53k antigen: A possible role for 53k in normal cells. Virol. 112:785, (1981).
H. A. Armelin, M. C. S. Armelin, K. Kelly, T. Stewart, P. Leder, B. K. Cochran, and C. D. Stiles. A functional role for c-myc in the mitogenic response to platelet-derived growth factor. Nature 310:655, (1984).
L. Kaczmarek, J. K. Hyland, R. Watt, M. Rosenberg, and R. Baserga. Microinjected c-myc as a competence factor. Science 228:1313, 1985.
W. E. Mercer, D. Nelson, A. B. DeLeo, L. J. Old, and R. Baserga. Microinjection of monoclonal antibody to protein p53 inhibits serum-induced DNA synthesis in 3T3 cells. Proc. Natl. Acad. Sci. USA 79:6309, (1982).
J. C. Reed, P. C. Nowell, and R. G. Hoover. Regulation of c-myc mRNA levels in normal human lymphocytes by modulators of cell proliferation. Proc. Natl. Acad. Sci. USA 82:4221. (1985).
J. A. Kern, R. P. Daniele, and P. C. Nowell. Accessory cells provide more than one signal for lectin mitogen-stimulated proliferation of human lymphocytes. J. Leukocyte Biol. 38:495, (1985).
J. C. Reed, D. E. Sabath, R. G. Hoover, and M. B. Prystowsky. Recombinant interleukin 2 regulates levels of c-myc mRNA in a cloned murine T lymphocyte. Mol. CellBiol. 5:3361, (1985).
S. Pan, and C. B. Knowles. Monoclonal antibody to SV40 T antigen blocks lysis of cloned cytolytic T cell line specific for SV40 TASA. Virol. 125:1, (1983).
J. C. Reed, J. D. Alpers, P. C. Nowell, and R. G. Hoover. Sequential expression of proto-oncogenes occurs during normal T lymphocyte mitogenesis. Proc. Natl. Acad. Sci. USA (1986), in press.
M. B. Prystowsky, G. Otten, S. K. Pierce, J. Shay, J. Olshon, and F. W. Fitch. Lymphokine production by cloned T lymphocytes. In: Lymphokines, ed. E. Pick, Academic Press. New York, 12:13, (1985).
J. M. Depper, W. J. Leonard, C. Drogula, M. Kronke, T. A. Waldmann, and W. C. Greene. Interleukin 2 (IL-2) augments transcription of the IL-2 receptor gene. Proc. Natl. Acad. Sci. USA 82:4230, (1985).
W. L. Farrar, S. W. Evan, F. W. Ruscetti, E. Bonvinni, H. A. Young, and B. M. Sparks. Biochemical mechanisms of interleukin 2 regulation of lymphocyte growth. In: Leukocytes and Host Defense, ed. J.J. Oppenheim, D.M. Jacobs, Alan R. Liss, New York, 5:75, (1986).
L. Kaczmarek, Oren, and R. Baserga. Co-operation between the p53 protein tumor antigen and platelet-poor plasma in the induction of cellular DNA synthesis. Exp. Cell Res. (1986), in press.
J. R. Feramisco, M. Gross, T. Kameta, Rosenberg, and R. W. Sweet. Microinjection of the oncogene form of the human H-ras (T-24) protein results in rapid proliferation of quiescent cells. Cell 38:109, (1984).
E. Muller, R. Bravo, J. Burckhardt, and T. Curran. Induction of c-fos gene and protein by growth factors precedes activation of c-myc. Nature 312:716, (1984).
W. J. Pledger, C. D. Stiles, H. N. Antoniades, and C. D. Scher. An ordered sequence of events is required before BALB/C-3T3 cells become committed to DNA synthesis. Proc. Natl. Acad. Sci. USA 75:2839, (1978).
N. Kitamura, A. Kitamura, K. Toyoshima, Y. Hirayama, and M. Yoshida. Avaian sarcoma virus Y73 genome sequence and structural similarity of its transforming gene product to that of Rous sarcoma virus. Nature 297:205, (1982).
I. G. Macara. Oncogenes, ions, and phospholipids. Am. J. Physiol. 248:C3, (1985).
T. R. Malek, C. Chan, L. H. Glimcher, R. N. Germain, and E. Shevach. Influence of accessory cell and T cell surface antigens in mitogen induced IL-2 receptor expression. J. Immunol. 135:1826. (1985).
J. C. Reed, R. J. Robb, W. C. Greene, and P. C. Nowell. Effect of wheat germ agglutinin on the interleukin pathway of human T-lymphocyte activation. J. Immunol. 134:314, (1985).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1987 Plenum Press, New York
About this chapter
Cite this chapter
Reed, J.C., Prystowsky, M.B., Kern, J.A., Alpers, J.D., Nowell, P.C., Hoover, R.G. (1987). Regulation of Proto-Oncogene Expression During T Lymphocyte Activation and Proliferation. In: Gupta, S., Paul, W.E., Fauci, A.S. (eds) Mechanisms of Lymphocyte Activation and Immune Regulation. Advances in Experimental Medicine and Biology, vol 213. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5323-2_25
Download citation
DOI: https://doi.org/10.1007/978-1-4684-5323-2_25
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-5325-6
Online ISBN: 978-1-4684-5323-2
eBook Packages: Springer Book Archive