Identification of a Novel Thymocyte Growth Factor Derived from B Cell Lymphomas

  • Takashi Suda
  • Ian MacNeil
  • Melissa Fischer
  • Kevin W. Moore
  • Albert Zlotnik
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 292)


T cell ontogeny is a rapidly developing area. However, the signals that mediate the differentiation and growth of immature T cells in the thymus through different maturational stages remain largely unknown. While much has been accomplished in understanding the role that molecules of the major histocompatibility complex have in the process of selection of the T cell repertoire,1,2 little is known about the role that cytokines may play in these processes. Most of these studies have focused on IL-2;3,4 however, its role in T cell ontogeny is still controversial. More recently, it has been observed that IL-4 can induce thymocyte growth in combination with phorbol ester (PMA).5,6 Other cytokines that have been shown to have thymocyte growth factor properties include IL-1,7 IL-6,8,9 IL-7,10 TNFa,11,12 and in fetal thymocytes (day 15 of gestation) P40 (IL-9)13 and GM-CSF.14 Many of these cytokines have been shown to be produced by thymocytes and/or thymic stromal cells as well,13,15 suggesting that they play a role in T cell ontogeny. We have been exploring the response patterns of adult murine thymocyte subsets separated on the basis of their expression of CD3, CD4 and CD8, and in fetal thymocytes at day 15 of gestation. An important conclusion from these studies is that the growth-promoting effects of some of these cytokines are specific for certain thymocyte subsets. For example, IL-1 is specific for the CD3+4-8- subset while IL-6 is specific for the CD4+8- and CD4-8+ subsets.8,12 These studies have shown that very few cytokine combinations induce the proliferation of the most immature thymocyte subset: CD3-4-8- thymocytes.12 Therefore, we have endeavored to find other novel cytokines that may activate this subset.


Cell Lymphoma Single Positive Immature Thymocyte Inhibit Cytokine Production Thymic Stromal Cell 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    J. Kappler, N. Roehm, and P. Marrack, T cell tolerance by cloncal elimination in the thymus, Cell 49:273 (1987).PubMedCrossRefGoogle Scholar
  2. 2.
    P. Kisielow, H. Teh, H. Bluthmann, and H. von Boehmer, Positive selection of antigen-specific T cells in the thymus by restricting MHC molecules, Nature 332:730 (1988).CrossRefGoogle Scholar
  3. 3.
    R. Palacios and H. von Boehmer, Requirements for growth of immature thymocytes from fetal and adult mice in vitro, Eur. J. Immunol. 16:12 (1986).PubMedCrossRefGoogle Scholar
  4. 4.
    R. Raulet, Expression and function of interleukin-2 receptors on immature thymocytes, Nature 314:101 (1985).PubMedCrossRefGoogle Scholar
  5. 5.
    A. Zlotnik, J. Ransom, F. Frank, M. Fischer, and M. Howard, Interleukin 4 is a growth factor for activated thymocytes: possible role in T cell ontogeny, Proc. Natl. Acad. Sci. USA 84:3856 (1987).PubMedCrossRefGoogle Scholar
  6. 6.
    R. Palacios, P. Sideras, and H. von Boehmer, Recombinant interleukin 4 promotes growth and differentiation of intrathymic T cell precursors from fetal mice in vitro, EMBO J. 6:91 (1987).PubMedGoogle Scholar
  7. 7.
    P. Conlon, C. Henney, and S. Gillis, Cytokine-dependent thymocyte responsess: Characterization of IL-1 and IL-2 target subpopulations and mechanism of action, J. Immunol. 128:797 (1982).PubMedGoogle Scholar
  8. 8.
    P. Hodgkin, J. Cupp, A. Zlotnik, and M. Howard, IL-2, IL-6 and IFNhave distinct effects on the IL-4 plus PMA induced proliferation of thymocyte subpopulations, Cell Immunol. 126:5 (1990).CrossRefGoogle Scholar
  9. 9.
    W. F. Chen, M. Fischer, G. Frank, and A. Zlotnik, Distinct patterns of lymphokine requirement for the proliferation of various subpopulations of activated thymocytes in a single cell assay, J. Immunol. 143:1598 (1989).PubMedGoogle Scholar
  10. 10.
    R. Murray, T. Suda, N. Wrighton, F. Lee, and A. Zlotnik, IL-7 is a growth and maintenance factor for mature and immature thymocyte subsets, Intl. Immunol. 1:526 (1989).CrossRefGoogle Scholar
  11. 11.
    G. E. Ranges, A. Zlotnik, T. Espevik, C. Dinarello, A. Cerami, and M. Palladino, Tumor necrosis factor /cachectin is a growth factor for thymocytes, J. Exp. Med. 167:1472 (1988).PubMedCrossRefGoogle Scholar
  12. 12.
    T. Suda, R. Murray, C. Guidos, and A. Zlotnik, Growth promoting activity of IL-1, IL-6, and TNF in combination with IL-2, IL-4 or IL-7 on murine thymocytes: Differential effects on CD4/CD8 subsets and on CD3+/CD3-double negative thymocytes, J. Immunol 144:3039 (1990).PubMedGoogle Scholar
  13. 13.
    T. Suda, R. Murray, M. Fisher, T. Yokota, and A. Zlotnik, Tumor necrosis factor a and P40 induce day 15 murine fetal thymocyte proliferation in combination with Interleukin 2, J. Immunol. 144: 1783 (1990).PubMedGoogle Scholar
  14. 14.
    T. Suda, A. O’Garra, I. MacNeil, M. Fischer, M. Bond, and A. Zlotnik, Identification of a novel thymocyte growth promoting factor derived from B cell lymphomas Cell Immunol. 129:228 (1990).CrossRefGoogle Scholar
  15. 15.
    J. Ransom, M. Fischer, T. Mosmann, T. Yokota, D. DeLuca, J. Schumacher, and A. Zlotnik, Interferon-is produced by activated immature thymocytes: Effects on la induction on thymic epithelial cells and on interleukin-4-mediated immature thymocyte proliferation, J. Immunol. 139:4102 (1987).PubMedGoogle Scholar
  16. 16.
    P. Willoughby, J. Jenette, and G. Haughton, Analysis of a murine B cell lymphoma, CH44, with an associated non-neoplastic T cell population. I. Proliferation of normal T lymphocytes is induced by a secreted product of the malignant B cells, J. Pathol. 133:507 (1988).Google Scholar
  17. 17.
    D. Fiorentino, M. Bond, and T. Mosmann, Two types of mouse helper T cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Thl clones, J. Exp. Med. 170:2081 (1989).PubMedCrossRefGoogle Scholar
  18. 18.
    K. Moore, P. Vieira, D. Fiorentino, M. Trounstine, T. Khan, and T. Mosmann, Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRF1, Science 248:1230 (1990).PubMedCrossRefGoogle Scholar
  19. 19.
    A. O’Garra, G. Stapleton, V. Dhar, M. Pearce, J. Schumacher, H. Rugo, D. Barbis, A. Stall, J. Cupp, K. Moore, P. Vieira, T. Mossman, A. Whitmore, L. Arnold, G. Haughton, and M. Howard, Production of known and novel cytokines by mouse B lymphomas and normal Ly-l+ B cells Internat. Immunol ,(in press).Google Scholar
  20. 20.
    I. MacNeil, T. Suda, K. Moore, T. Mossman, and A. Zlotnik, Interleukin 10: A novel cytokine growth cofactor for mature and immature murine lymphocytes (submitted for publication).Google Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Takashi Suda
    • 1
  • Ian MacNeil
    • 1
  • Melissa Fischer
    • 1
  • Kevin W. Moore
    • 1
  • Albert Zlotnik
    • 1
  1. 1.Department of ImmunologyDNAX Research Institute of Molecular and Cellular BiologyPalo AltoUSA

Personalised recommendations