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.
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
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.
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.
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.
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.
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.
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.
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.
Henney, C. S. (1989) Interleukin 7: effects on early events in lymphopoiesis. Immunol. Today 10, 170–173.
Kunisada, T., Ogawa, M., Hayashi, S., Era, T., and Nishikawa, S. (1992) Interleukin-7 and B lymphopoiesis. Chem. Immunol. 51, 205–235.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Poussier, P. and Julius, M. (1994) Thymus independent T cell development and selection in the intestinal epithelium. Annu. Rev. Immunol. 12, 521–553.
Lefrancois, L. (1991) Phenotypic complexity of intraepithelial lymphocytes of the small intestine. J. Immunol. 147, 1746–1751.
Guy, G. D. and Vassalli, P. (1993) Gut intraepithelial T lymphocytes. Curr. Opin. Immunol. 5, 247–252.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Kuhn, R., Rajewsky, K., and Muller, W. (1991) Generation and analysis of interleukin-4 deficient mice. Science 254, 707–710.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Editor information
Editors and Affiliations
Rights 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