Skip to main content

IL-7 Knockout Mice and the Generation of Lymphocytes

  • Chapter
Book cover Cytokine Knockouts

Part of the book series: Contemporary Immunology ((CONTIM))

Abstract

A common theme in the molecular interaction between cytokines and their receptors is that an individual cytokine binds a receptor complex. In general, this requires a cytokine-specific receptor subunit and a “common” receptor subunit. The common subunit is, by definition, shared among numerous cytokines. The result is a grouping of cytokines into families that all require a particular common subunit for high-affinity binding and signal transduction. This is well exemplified by the cytokine grouping of interleukin (IL)-2, IL-4, IL-7, IL-9, and IL-15 (1–7). Each of these cytokines binds, at minimum, a cytokine-specific subunit as well as a common subunit, referred to in this chapter as the common gamma (γc) chain. Subsequent to the binding of a cytokine to its corresponding receptor complex, signal transduction events, including the Jak/STAT pathway, deliver a signal for a biological response of the cell. Since IL-7 has been extensively reviewed elsewhere (8,9), this chapter is not an exhaustive description of IL-7 from cloning to present, focusing instead on IL-7 related biology learned from the gene knockout model and how these observations integrate into other gene knockout studies of cytokines and receptors defined by the γc chain receptor. We summarize published work as well as refer to and provide brief descriptions of current experiments.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 74.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Takeshita, T., Asao, H., Ohtani, K., Ishii, N., Kumaki, S., Tanaka, N., Munakata, H., Nakamura, M., and Sugamura, K. (1992) Cloning of the gamma chain of the human IL-2 receptor. Science 257, 379–382.

    Article  PubMed  CAS  Google Scholar 

  2. Russell, S. M., Keegan, A. D., Harada, N., Nakamura, Y., Noguchi, M., Leland, P., Friedmann, M. C., Miyajima, A., Puri, R. K., Paul, W. E., and Leonard, W. L. (1993) Interleukin-2 receptor gamma chain: a functional component of the interleukin-4 receptor. Science 262, 1880–1883.

    Article  PubMed  CAS  Google Scholar 

  3. Kondo, M., Takeshita, T., Ishii, N., Nakamura, M., Watanabe, S., Arai, K., and Sugamura, K. (1993) Sharing of the interleukin-2 (IL-2) receptor gamma chain between receptors for IL-2 and IL-4. Science 262, 1874–1877.

    Article  PubMed  CAS  Google Scholar 

  4. Noguchi, M., Nakamura, Y., Russell, S. M., Ziegler, S. F., Tsang, M., Cao, X., and Leonard, W. J. (1993) Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor. Science 262, 1877–1880.

    Article  PubMed  CAS  Google Scholar 

  5. Russell, S. M., Johnston, J. A., Noguchi, M., Kawamura, M., Bacon, C. M., Friedmann, M., Berg, M., Mcvicar, D. W., Witthuhn, B. A., Silvennoinen, O., Goldman, A. S., Schmalstieg, F. C., le, J. N., Oshea, J. J., and Leonard, W. J. (1994) Interaction of il-2r-beta and gamma(c) chains with jakl and jak3—implications for xscid and xcid. Science 266, 1042–1045.

    Article  PubMed  CAS  Google Scholar 

  6. Kimura, Y., Takeshita, T., Kondo, M., Ishii, N., Nakamura, M., Van, S. J., and Sugamura, K. (1995) Sharing of the IL-2 receptor gamma chain with the functional IL-9 receptor complex. Int. Immunol. 7, 115–120.

    Article  PubMed  CAS  Google Scholar 

  7. Giri, J. G., Ahdieh, M., Eisenman, J., Shanebeck, K., Grabstein, K., Kumaki, S., Namen, A., Park, L. S., Cosman, D., and Anderson, D. (1994) Utilization of the beta and gamma chains of the IL-2 receptor by the novel cytokine IL-15. Embo J. 13, 2822–2830.

    PubMed  CAS  Google Scholar 

  8. Henney, C. S. (1989) Interleukin 7: effects on early events in lymphopoiesis. Immunol. Today 10, 170–173.

    Article  PubMed  CAS  Google Scholar 

  9. Kunisada, T., Ogawa, M., Hayashi, S., Era, T., and Nishikawa, S. (1992) Interleukin-7 and B lymphopoiesis. Chem. Immunol. 51, 205–235.

    Article  PubMed  CAS  Google Scholar 

  10. Namen, A. E., Lupton, S., Hjerrild, K., Wignall, J., Mochizuki, D. Y., Schmierer, A., Mosley, B., March, C. J., Urdal, D., Gillis, S., Cosman, D., and Goodwin, R. G. (1988) Stimulation of B-cell progenitors by cloned murine interleukin-7. Nature 333, 571–573.

    Article  PubMed  CAS  Google Scholar 

  11. Namen, A. E., Schmierer, A. E., March, C. J., Overell, R. W., Park, L. S., Urdal, D. L., and Mochizuki, D. Y. (1988) B cell precursor growth-promoting activity. Purification and characterization of a growth factor active on lymphocyte precursors. J. Exp. Med. 167, 988–1002.

    Article  PubMed  CAS  Google Scholar 

  12. Takeda, S., Gillis, S., and Palacios, R. (1989) In vitro effects of recombinant interleukin 7 on growth and differentiation of bone marrow pro-B- and proT-lymphocyte clones and fetal thymocyte clones. Proc. Natl. Acad. Sci. USA 86, 1634–1638.

    Article  PubMed  CAS  Google Scholar 

  13. Suda, T., Okada, S., Suda, J., Miura, Y., Ito, M., Sudo, T., Hayashi, S., Nishikawa, S., and Nakauchi, H. (1989) A stimulatory effect of recombinant murine interleukin-7 (IL-7) on B-cell colony formation and an inhibitory effect of IL-1 alpha. Blood 74, 1936–1941.

    PubMed  CAS  Google Scholar 

  14. Saeland, S., Duvert, V., Pandrau, D., Caux, C., Durand, I., Wrighton, N., Wideman, J., Lee, F., and Banchereau, J. (1991) Interleukin-7 induces the proliferation of normal human B-cell precursors. Blood 78, 2229–2238.

    PubMed  CAS  Google Scholar 

  15. Murray, R., Suda, T., Wrighton, N., Lee, F., and Zlotnik, A. (1989) IL-7 is a growth and maintenance factor for mature and immature thymocyte subsets. Int. Immunol. 1, 526–531.

    Article  PubMed  CAS  Google Scholar 

  16. Watson, J. D., Morrissey, P. J., Namen, A. E., Conlon, P. J., and Widmer, M. B. (1989) Effect of IL-7 on the growth of fetal thymocytes in culture. J. Immunol. 143, 1215–1222.

    PubMed  CAS  Google Scholar 

  17. Conlon, P. J., Morrissey, P. J., Nordan, R. P., Grabstein, K. H., Prickett, K. S., Reed, S. G., Goodwin, R., Cosman, D., and Namen, A. E. (1989) Murine thymocytes proliferate in direct response to interleukin-7. Blood 74, 1368–1373.

    Google Scholar 

  18. Grabstein, K. H., Waldschmidt, T. J., Finkelman, F. D., Hess, B. W., Alpert, A. R., Boiani, N. E., Namen, A. E., and Morrissey, P. J. (1993) Inhibition of murine B and T lymphopoiesis in vivo by an anti-interleukin 7 monoclonal antibody. J. Exp. Med. 178, 257–264.

    Google Scholar 

  19. Samaridis, J. Casorati, G., Traunecker, A., Iglesias, A., Gutierrez, J. C., Muller, U., and Palacios, R. (1991) Development of lymphocytes in interleukin 7-transgenic mice. Eur. J. Immunol. 21 453–460.

    Google Scholar 

  20. Uehira, M., Matsuda, H., Hikita, I., Sakata, T., Fujiwara, H., and Nishimoto, H. (1993) The development of dermatitis infiltrated by gamma delta T cells in IL-7 transgenic mice. Int. Immunol. 5, 1619–1627.

    Article  PubMed  CAS  Google Scholar 

  21. Rich, B. E., Campos, T. J., Tepper, R. I., Moreadith, R. W., and Leder, P. (1993) Cutaneous lymphoproliferation and lymphomas in interleukin 7 transgenic mice. J. Exp. Med. 177, 305–316.

    Article  PubMed  CAS  Google Scholar 

  22. von Freeden-Jeffry, U., Vieira, P., Lucian, L. A., McNeil, T., Burdach, S. E., and Murray, R. (1995) Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine. J. Exp. Med. 181, 1519–1526.

    Article  PubMed  CAS  Google Scholar 

  23. Hardy, R. R., Carmack, C. E., Shinton, S. A., Kemp, J. D., and Hayakawa, K. (1991) Resolution and characterization of pro-B and pre-pro-B cell stages in normal mouse bone marrow. J. Exp. Med. 173, 1213–1225.

    Article  PubMed  CAS  Google Scholar 

  24. Poussier, P. and Julius, M. (1994) Thymus independent T cell development and selection in the intestinal epithelium. Annu. Rev. Immunol. 12, 521–553.

    Article  PubMed  CAS  Google Scholar 

  25. Lefrancois, L. (1991) Phenotypic complexity of intraepithelial lymphocytes of the small intestine. J. Immunol. 147, 1746–1751.

    PubMed  CAS  Google Scholar 

  26. Guy, G. D. and Vassalli, P. (1993) Gut intraepithelial T lymphocytes. Curr. Opin. Immunol. 5, 247–252.

    Article  Google Scholar 

  27. Mosley, R. L. and Klein, J. R. (1992) Peripheral engraftment of fetal intestine into athymic mice sponsors T cell development: direct evidence for thymopoietic function of murine small intestine. J. Exp. Med. 176, 1365–1373.

    Article  PubMed  CAS  Google Scholar 

  28. Moore, T. A., von Freeden, J. V., Murray, R., and Zlotnik, A. (1996) Inhibition of yS T-cell development and early reactivation in IL-7–1-mice. J. Imminol. 157, 2366–2373.

    CAS  Google Scholar 

  29. Muegge, K., Vila, M. P., and Dumm, S. K. (1993) Interleukin-7 • a cofactor for V(D)J rearrangement of the T cell receptor beta gene. Science 261, 93–95.

    Article  PubMed  CAS  Google Scholar 

  30. Allison, J. P. and Havran, W. L. (1991) The immunobiology of T cells with invariant gamma delta antigen receptors. Annu. Rev. Immunol. 9, 679–705.

    Article  PubMed  CAS  Google Scholar 

  31. Leclercq, G., Plum, J., Nandi, D., De, S. M., and Allison, J. P. (1993) Intrathymic differentiation of V gamma 3 T cells. J. Exp. Med. 178, 309–315.

    Article  PubMed  CAS  Google Scholar 

  32. Appasamy, P. M. (1992) IL 7-induced T cell receptor-gamma gene expression by pre-T cells in murine fetal liver cultures. J. Immunol. 149, 1649–1656.

    PubMed  CAS  Google Scholar 

  33. Appasamy, P. M., Kenniston, T. J., Weng, Y., Holt, E. C., Kost, J., and Chambers, W. H. (1993) Interleukin 7-induced expression of specific T cell receptor gamma variable region genes in murine fetal liver cultures. J. Exp. Med. 178, 2201–2206.

    Article  PubMed  CAS  Google Scholar 

  34. Maki, K., Sunaga, S., and Ikuta, K. (1996). The V-J Recombination of T-cell Receptor -y genes is blocked in Interleukin-7 Receptor-deficient mice J. Exp. Med. 184, 2423–2427.

    Article  PubMed  CAS  Google Scholar 

  35. Schorle, H., Holtschke, T., Hunig, T., Schimpl, A., and Horak, I. (1991) Development and function of T cells in mice rendered interleukin-2 deficient by gene targeting. Nature 352, 621–624.

    Article  PubMed  CAS  Google Scholar 

  36. Kuhn, R., Rajewsky, K., and Muller, W. (1991) Generation and analysis of interleukin-4 deficient mice. Science 254, 707–710.

    Article  PubMed  CAS  Google Scholar 

  37. Sadlack, B., Kuhn, R., Schorle, H., Rajewsky, K., Muller, W., and Horak, I. (1994) Development and proliferation of lymphocytes in mice deficient for both interleukins-2 and -4. Eur. J. Immunol. 24, 281–284.

    Article  PubMed  CAS  Google Scholar 

  38. Noguchi, M., Yi, H., Rosenblatt, H. M., Filipovich, A. H., Adelstein, S., Modi, W. S., McBride, O. W., and Leonard, W. J. (1993) Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans. Cell 73, 147–157.

    Article  PubMed  CAS  Google Scholar 

  39. DiSanto, J. P., Müller, W., Guy, G. D., Fischer, A., and Rajewsky, K. (1995) Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor gamma chain. Proc. Natl. Acad. Sci. USA 92, 377–381.

    Article  PubMed  CAS  Google Scholar 

  40. Cao, X., Shores, E. W., Hu, L. J., Anver, M. R., Kelsall, B. L., Russell, S. M., Drago, J., Noguchi, M., Grinberg, A., Bloom, E. T., et al. (1995) Defective lymphoid development in mice lacking expression of the common cytokine receptor gamma chain. Immunity 2, 223–238.

    Article  PubMed  CAS  Google Scholar 

  41. Peschon, J. J., Morrissey, P. J., Grabstein, K. H., Ramsdell, F. J., Maraskovsky, E., Gliniak, B. C., Park, L. S., Ziegler, S. F., Williams, D. E., Ware, C. B., Meyer, J. D., and Davison, B. L. (1994) Early lymphocyte expansion is severely impaired in interleukin-7 receptor-deficient mice. J. Exp. Med. 180, 1955–1960.

    Google Scholar 

  42. Sudo, T., Nishikawa, S., Ohno, N., Akiyama, N., Tamakoshi, M., Yoshida, H., and Nishikawa, S. (1993) Expression and function of the interleukin 7 receptor in mutine lymphocytes. Proc. Natl. Acad. Sci. USA 90, 9125–9129.

    Google Scholar 

  43. Lin, J. X., Migone, T. S., Tsang, M., Friedmann, M., Weatherbee, J. A., Zhou, L., Yamauchi, A., Bloom, E. T., Mietz, J., John, S., and et al. (1995) The role of shared receptor motifs and common Stat proteins in the generation of cytokine pleiotropy and redundancy by IL-2, IL-4, IL-7, IL-13, and IL-15. Immunity 2, 331–339.

    Article  PubMed  CAS  Google Scholar 

  44. Miyazaki, T., Kawahara, A., Fujii, H., Nakagawa, Y., Minami, Y., Liu, Z. J., Oishi, I., Silvennoinen, O., Witthuhn, B. A., Ihle, J. N., and et al. (1994) Functional activation of Jakl and Jak3 by selective association with IL-2 receptor subunits. Science 266, 1045–1047.

    Google Scholar 

  45. Carson, W. E., Giri, J. G., Lindemann, M. J., Linett, M. L., Ahdieh, M., Paxton, R., Anderson, D., Eisenmann, J., Grabstein, K., and Caligiuri, M. A. (1994) Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor. J. Exp. Med. 180, 1395–1403.

    Article  PubMed  CAS  Google Scholar 

  46. Grabstein, K. H., Eisenman, J., Shanebeck, K., Rauch, C., Srinivasan, S., Fung, V., Beers, C., Richardson, J., Schoenborn, M. A., Ahdieh, M., and et al. (1994) Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor. Science 264, 965–968.

    Article  PubMed  CAS  Google Scholar 

  47. Maki, K., Sunaga, S., Komagata, Y., Kodaira, Y., Mabuchi, A., Karasuyama, H, Yokomuro, K., Miyazaki, J., and Ikuta, K. (1996) Interleukin 7 receptor-deficient mice lack y6 cells. Proc. Natl. Acad. Sci. USA 93, 7172–7177.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer Science+Business Media New York

About this chapter

Cite this chapter

von Freeden-Jeffry, U., Moore, T.A., Zlotnik, A., Murray, R. (1998). IL-7 Knockout Mice and the Generation of Lymphocytes. In: Durum, S.K., Muegge, K. (eds) Cytokine Knockouts. Contemporary Immunology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4757-2753-1_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-2753-1_2

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-2755-5

  • Online ISBN: 978-1-4757-2753-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics