Mechanisms in Interleukin 3 Regulated Growth and Differentiation

  • James N. Ihle
  • Yacob Weinstein
  • Ulf R. Rapp
  • John L. Cleveland
  • E. Premkumar Reddy
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 213)


The immune system regulates the growth and differentiation of a variety of hematopoietic and lymphoid lineages through the production of a series of lymphokines by activated T cells. Among these interleukin-2 (IL-2) has been the most extensively studied and has been shown to support the proliferation of activated T cells. The major colony stimulating factor produced by activated T cells, a granulocyte-macrophage colony stimulating factor (GM-CSF), supports the proliferation and terminal differentiation of cells committed to the myeloid lineage. B-cell stimulating factor (BSF-1) supports proliferation of activated B cells and may induce the proliferation of a variety of additional cell types. In contrast to these factors, which primarily act on mature cells, interleukin-3 (IL-3) acts on relatively immature hematopoietic/lymphoid cells.


Mast Cell Myeloid Cell Line Fetal Liver Cell Avian Myeloblastosis Virus Myeloid Leukemia Cell Line 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    J. N. Ihle, L. Pepersack and L. Rebhar. Regulation of T cell differentiation: In vitro induction of 20 alpha hydroxysteroid dehydrogenase in splenic lymphocytes is mediated by a unique lymphokine. J. Immunol. 126:2184, (1981).Google Scholar
  2. 2.
    J. N. Ihle, J. Keller, S. Oroszlan, L. Henderson, T. Copeland, F. Fitch, M. B. Prystowsky, E. Goldwasser, J. S. Schrader, E. Palazynski, M. Dy, and B. Lebel. Biological properties of homogeneous interleukin 3: I. Demonstration of WEHI-3 growth factor activity, mast cell growth factor activity, P-cell stimulating factor activity, colony stimulating factor activity. J. Immunol. 131:282, (1983).Google Scholar
  3. 3.
    M. B. Prystowsky, M. F. Naujokas, J. N. Ihle, E. Goldwasser, and F. W. Fitch. A microassay for colony-stimulating factor based on thymidine incorporation. Amer. J. Pathol. 114:149, (1984).Google Scholar
  4. 4.
    M. C. Fung, A. J. Hapel, S. Ymer, D. R. Cohen, R. M. Johnson, H. D. Campbell, and I. G. Young. Molecular cloning of cDNA for murine interleukin-3. Nature 307:233, (1984).ADSCrossRefGoogle Scholar
  5. 5.
    T. Yokota, F. Lee, D. Rennick, C. Hall, N. Arai, T. Mosmann, G. Nable, H. Cantor, and K. Arai. Isolation and characterization of a mouse cDNA clone that expresses mast cell growth factor activity in monkey cells. Proc. Natl. Acad. Sci. USA 81:1070, (1984).ADSCrossRefGoogle Scholar
  6. 6.
    I. Clark-Lewis, R. Aebersold, H. Ziltener, J. W. Schrader, L. E. Hood, and S. B. H. Kent. Automated chemical synthesis of a protein growth factor for hemopoietic cells, interleukin 3. Science 231:134, (1985).ADSCrossRefGoogle Scholar
  7. 7.
    J. N. Ihle, A. Rein, and R. Mural. Immunological and virological mechanisms in retrovirus induced murine leukemogenesis. In Advances in Viral Oncology, G. Klein ed. Raven Press, New York, (1984) pp 95.Google Scholar
  8. 8.
    J. C. Lee, and J. N. Ihle. Increased responses to lymphokines are diagnostic of preleukemia in Moloney virus inoculated mice. Proc. Natl. Acad. Sci. USA 78:7712, (1981).ADSCrossRefGoogle Scholar
  9. 9.
    J. C. Lee, and J. N. Ihle. Chronic immune stimulating is required for Moloney leukemia virus-induced lymphomas. Nature 209:P407, (1981).ADSCrossRefGoogle Scholar
  10. 10.
    K. L. Holmes, E. Palaszynski, H. C. Morse III, and J. N. Ihle. Mechanisms in neoplasias induced by Cas-Br-M murine leukemia virus. II. A high frequency of interleukin-3 dependent cell lines are derived from myeloid and erythroid leukemias. Proc. Natl. Acad. Sci. USA 82:6687, (1985).ADSCrossRefGoogle Scholar
  11. 11.
    J. L. Spivak, R. R. L. Smith, and J. N. Ihle. Interleukin 3 promotes the in vitro proliferation of murine pluripotent hematopoietic stem cells. J. Clin. Invest. 76:1613, (1985).CrossRefGoogle Scholar
  12. 12.
    J. Keller, Y. Weinstein, M. Hursey, and J. N. Ihle. Interleukin 2 and 3 regulate the in vitro proliferation of two distinguishable populations of 20 alpha hydroxysteroid dehydrogenase positive cells. J. Immunol. 135:1864, (1985).Google Scholar
  13. 13.
    J. N. Ihle, J. Keller, A. Rein, J. Cleveland, and U. Rapp. Interleukin-3 regulation of the growth of normal and transformed hematopoietic cells: Cancer Cells 3/Growth Factors and Transformation. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, (1985) pp 211.Google Scholar
  14. 14.
    T. Suda, J. Suda, M. Ogawa, and J. N. Ihle. Permissive role of interleukin 3 (IL-3) in proliferation and differentiation of multipotential hemopoietic progenitors in culture. J. Clin. Physiol. 124:182. (1985).CrossRefGoogle Scholar
  15. 15.
    K. Koike, E. R. Stanley, J. N. Ihle, and M. Ogawa. Macrophage colony formation supported by purified CSF-1 and/or IL-3 in serum-free culture: Evidence for hierarchial difference in macrophage colony-forming cells. J. Cell. Physiol. in press.Google Scholar
  16. 16.
    J. N. Ihle, J. Keller, and R. Coffman. Characteristics of hematopoietic stem cell differentiation-induced in vitro by interleukin 3: Cell in “Defined” environments. Springer Verlag, Inc., New York, in press.Google Scholar
  17. 17.
    C. Moscovici, and L. Gazzola. Transformation of hematopoietic cells with avian leukemia viruses: Advances in Viral Oncology. Raven Press, New York, (1982).Google Scholar
  18. 18.
    K. H. Klempnauer, G. Ramsey, J. M. Bishop, M. G. Moscovici, C. Moscovici, J. P. McGrath, and A. D. Levinson. The product of the retroviral transforming gene v-myb is a truncated version of the protein encoded by the cellular oncogene c-myb. Cell 33:345, (1983).CrossRefGoogle Scholar
  19. 19.
    Y. Weinstein, J. N. Ihle, S. Lavu, and E. P. Reddy. Truncation of the c-mvb gene by a retroviral integration in an interleukin-3 dependent myeloid leukemia cell line. Proc. Natl. Acad. Sci. USA, in press.Google Scholar
  20. 20.
    Y. Weinstein, S. May, J. Cleveland, U. Rapp, and J. N. Ihle, In preparation.Google Scholar
  21. 21.
    H. Beug, A. Leutz, P. Kahn, and T. Graf. Ts mutants of E26 leukemia virus allow transformed myeloblasts, but not erythroblasts or fibroblasts, to differentiate at the nonpermissive temperature. Cell 39:579, (1984).CrossRefGoogle Scholar
  22. 22.
    H. Beug, M. J. Hayman, and T. Graf. Myeloblasts transformed by the avian acute leukemia virus E26 are hormone-dependent for growth and for the expression of putative myb-containing protein. The EMBO J. 1:1069, (1982).Google Scholar
  23. 23.
    G. L. Shen-Ong, M. Potter, J. F. Mushinski, S. Lavu, and E. P. Reddy. Activation of the c-myb locus by viral insertional mutagenesis in plasmacytoid lymphosarcomas. Science 226:1077, (1984).ADSCrossRefGoogle Scholar
  24. 24.
    J. F. Mushinski, M. Potter, S. R. Bauer, and E. P. Reddy. DNA rearrangement and altered RNA expression of the c-mvb oncogene in mouse plasmacytoid lymphosarcomas. Science 20:795. (1983).CrossRefGoogle Scholar
  25. 25.
    U. R. Rapp, J. L. Cleveland, K. Brightman, A. Scott, and J. N. Ihle. Abrogation of IL-3 and IL-2 dependence by recombinant murine retroviruses expression v-myc oncogenes. Nature 317:434, (1985).ADSCrossRefGoogle Scholar
  26. 26.
    E. Blasi, B. J. Mathieson, and L. Varesio. Selective immortalization of murine macrophages from fresh bone marrow by a raf/myc recombinant murine retrovirus. Nature 318:667, (1985).ADSCrossRefGoogle Scholar
  27. 27.
    T. M. Dexter, J. Garland, D. Scott, E. Scolnick, and D. Metcalf. Growth of factor-dependent hemopoietic precursor cell lines. J. Exp. Med. 152:1036, (1980).CrossRefGoogle Scholar
  28. 28.
    J. N. Ihle, A. Hapel, J. Greenberger, J. C. Lee, and A. Rein. Possible roles of interleukin 3 in the regulation of lymphocyte differentiation. In The Potential Role of T Cells in Cancer Therapy, A. Fefer and Al Goldstein eds. Raven Press, New York, (1982) pp92.Google Scholar
  29. 29.
    K. Kelly, B. H. Cochran, C. D. Stiles, and P. Leder. Cell-specific regulation of the c-mvc gene by lymphocyte mitogens and platelet-derived growth factor. Cell 35:685, (1985).Google Scholar
  30. 30.
    J. H. Pierce, M. Potter, A. Scott, A. Humphries, J. Aaronson, and J. N. Ihle. Abelson-MuLVG transformation of normal mast cells abrogates their dependence on IL-3 for growth. Cell 41:685, (1985).CrossRefGoogle Scholar
  31. 31.
    W. D. Cook, D. Metcalf, N. A. Nicola, A. W. Burgess, and F. Walter. Malignant transformation of a growth factor-dependent myeloid cell line by Abelson virus without evidence of an autocrine mechanism. Cell 41:677, (1985).CrossRefGoogle Scholar
  32. 32.
    A. Rein, D. R. Lowy, B. I. Gerwin, S. K. Ruscetti, and R. H. Bassin. Molecular properties of a gag- pol- env+ murine leukemia virus from cultured AKR leukemia cells. J. Virol. 41:626, (1982).Google Scholar
  33. 33.
    S. Ishii, G. T. Merlino, and I. Pastan. Promoter region of the human Harvey ras proto-oncogene: Similarity to the EGF receptor proto-oncogene promoter. Science 230:1378, (1985).ADSCrossRefGoogle Scholar
  34. 34.
    M. B. Palaszynski, and J. N. Ihle. Evidence for specific receptors for interleukin-3 on lymphokine dependent cell lines established from long-term bone marrow cultures. J. Immunol. 132:1872, (1984).Google Scholar
  35. 35.
    S. May, and J. N. Ihle. Affinity isolation of the interleukin 3 cell surface receptor. Biochem. Biophys. Res Communication, in press.Google Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • James N. Ihle
    • 1
  • Yacob Weinstein
    • 1
    • 2
  • Ulf R. Rapp
    • 3
  • John L. Cleveland
    • 3
  • E. Premkumar Reddy
    • 4
  1. 1.LBI-Basic Research Program, Frederick Cancer Research FacilityNational Cancer InstituteFredrickUSA
  2. 2.Faculty of Health Sciences, Unit of Microbiology and ImmunologyBen Gurion University of the NegevBeer ShevaIsrael
  3. 3.Laboratory of Viral CarcinogenesisNational Cancer InstituteRederickUSA
  4. 4.Department of Molecular BiologyHoffman-La Roche Institute of Molecular Biology, Inc.NutleyUSA

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