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Experimental Model for the Study of the Human Immune System

Production and Monitoring of “Human Immune System” Rag2−/−γc −/− Mice

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Book cover Innate Immunity

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 415))

Summary

Since the late 1980s, the study of the function and development of the human immune system has made intensive use of humanized animal models, among which mouse models have been proven extremely efficient and handy. Recent advances have lead to the establishment of new models with improved characteristics, both in terms of engraftment efficiency and in situ multilineage human hematopoietic development. In particular, the use of newborn BALB/c Rag2−/−γc −/− mice as recipients for human hematopoietic stem cells has proven particularly efficient. We describe here how to produce and monitor such “human immune system” (HIS) (BALB-Rag/γ) mice, which offer large prospects for experimental study of the human immune system and as a preclinical screening tool.

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References

  1. Greiner, D. L., Hesselton, R. A., and Shultz, L. D. SCID mouse models of human stem cell engraftment (1998) Stem Cells 16, 166–77.

    Article  CAS  PubMed  Google Scholar 

  2. Macchiarini, F., Manz, M. G., Palucka, A. K., and Shultz, L. D. Humanized mice: are we there yet? (2005) J Exp Med 202, 1307–11.

    Article  CAS  PubMed  Google Scholar 

  3. Legrand, N., Weijer, K., and Spits, H. Experimental models to study development and function of the human immune system in vivo (2006) J Immunol 176, 2053–8.

    CAS  PubMed  Google Scholar 

  4. McCune, J. M. Animal models of HIV-1 disease (1997) Science 278, 2141–2.

    Article  CAS  PubMed  Google Scholar 

  5. McCune, J. M., Namikawa, R., Kaneshima, H., Shultz, L. D., Lieberman, M., and Weissman, I. L. The SCID-hu mouse: murine model for the analysis of human hematolymphoid differentiation and function (1988) Science 241, 1632–9.

    Article  CAS  PubMed  Google Scholar 

  6. Krowka, J. F., Sarin, S., Namikawa, R., McCune, J. M., and Kaneshima, H. Human T cells in the SCID-hu mouse are phenotypically normal and functionally competent (1991) J Immunol 146, 3751–6.

    CAS  PubMed  Google Scholar 

  7. Hesselton, R. M., Greiner, D. L., Mordes, J. P., Rajan, T. V., Sullivan, J. L., and Shultz, L. D. High levels of human peripheral blood mononuclear cell engraftment and enhanced susceptibility to human immunodeficiency virus type 1 infection in NOD/LtSz-scid/scid mice (1995) J Infect Dis 172, 974–82.

    CAS  PubMed  Google Scholar 

  8. Larochelle, A., Vormoor, J., Hanenberg, H., Wang, J. C., Bhatia, M., Lapidot, T., Moritz, T., Murdoch, B., Xiao, X. L., Kato, I., Williams, D. A., and Dick, J. E. Identification of primitive human hematopoietic cells capable of repopulating NOD/SCID mouse bone marrow: implications for gene therapy (1996) Nat Med 2, 1329–37.

    Article  CAS  PubMed  Google Scholar 

  9. Kollet, O., Peled, A., Byk, T., Ben-Hur, H., Greiner, D., Shultz, L., and Lapidot, T. Beta2 microglobulin-deficient (B2m(null)) NOD/SCID mice are excellent recipients for studying human stem cell function (2000) Blood 95, 3102–5.

    CAS  PubMed  Google Scholar 

  10. Kerre, T. C., De Smet, G., De Smedt, M., Zippelius, A., Pittet, M. J., Langerak, A. W., De Bosscher, J., Offner, F., Vandekerckhove, B., and Plum, J. Adapted NOD/SCID model supports development of phenotypically and functionally mature T cells from human umbilical cord blood CD34(+) cells (2002) Blood 99, 1620–6.

    Article  CAS  PubMed  Google Scholar 

  11. Hiramatsu, H., Nishikomori, R., Heike, T., Ito, M., Kobayashi, K., Katamura, K., and Nakahata, T. Complete reconstitution of human lymphocytes from cord blood CD34+ cells using the NOD/SCID/gammacnull mice model (2003) Blood 102, 873–80.

    Article  CAS  PubMed  Google Scholar 

  12. Ishikawa, F., Livingston, A. G., Minamiguchi, H., Wingard, J. R., and Ogawa, M. Human cord blood long-term engrafting cells are CD34+ CD38 (2003) Leukemia 17, 960–4.

    Article  CAS  PubMed  Google Scholar 

  13. Traggiai, E., Chicha, L., Mazzucchelli, L., Bronz, L., Piffaretti, J. C., Lanzavecchia, A., and Manz, M. G. Development of a human adaptive immune system in cord blood cell-transplanted mice (2004) Science 304, 104–7.

    Article  CAS  PubMed  Google Scholar 

  14. Gimeno, R., Weijer, K., Voordouw, A., Uittenbogaart, C. H., Legrand, N., Alves, N. L., Wijnands, E., Blom, B., and Spits, H. Monitoring the effect of gene silencing by RNA interference in human CD34+ cells injected into newborn RAG2-/- gammac-/- mice: functional inactivation of p53 in developing T cells (2004) Blood 104, 3886–93.

    Article  CAS  PubMed  Google Scholar 

  15. Ishikawa, F., Yasukawa, M., Lyons, B., Yoshida, S., Miyamoto, T., Yoshimoto, G., Watanabe, T., Akashi, K., Shultz, L. D., and Harada, M. Development of functional human blood and immune systems in NOD/SCID/IL2 receptor γ chainnull mice (2005) Blood 106, 1565–73.

    Article  CAS  PubMed  Google Scholar 

  16. Chicha, L., Tussiwand, R., Traggiai, E., Mazzucchelli, L., Bronz, L., Piffaretti, J. C., Lanzavecchia, A., and Manz, M. G. Human adaptive immune system Rag2−/−γc −/− mice (2005) Ann N Y Acad Sci 1044, 236–43.

    Article  CAS  PubMed  Google Scholar 

  17. Schotte, R., Nagasawa, M., Weijer, K., Spits, H., and Blom, B. The ETS transcription factor Spi-B is required for human plasmacytoid dendritic cell development (2004) J Exp Med 200, 1503–9.

    Article  CAS  PubMed  Google Scholar 

  18. Legrand, N., Cupedo, T., van Lent, A. U., Ebeli, M. J., Weijer, K., Hanke, T., and Spits, H. Transient accumulation of human mature thymocytes and regulatory T cells with CD28 superagonist in “human immune system” Rag2−/−γc −/− mice (2006) Blood 108, 238–45.

    Article  CAS  PubMed  Google Scholar 

  19. Mombaerts, P., Iacomini, J., Johnson, R. S., Herrup, K., Tonegawa, S., and Papaioannou, V. E. RAG-1-deficient mice have no mature B and T lymphocytes (1992) Cell 68, 869–77.

    Article  CAS  PubMed  Google Scholar 

  20. Shinkai, Y., Rathbun, G., Lam, K. P., Oltz, E. M., Stewart, V., Mendelsohn, M., Charron, J., Datta, M., Young, F., Stall, A. M., et al. RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement (1992) Cell 68, 855–67.

    Article  CAS  PubMed  Google Scholar 

  21. Cao, X., Shores, E. W., Hu-Li, J., Anver, M. R., Kelsall, B. L., Russell, S. M., Drago, J., Noguchi, M., Grinberg, A., Bloom, E. T., Paul, W. E., Katz, S. I., Love, P. E., and Leonard, W. J. Defective lymphoid development in mice lacking expression of the common cytokine receptor gamma chain (1995) Immunity 2, 223–38.

    Article  CAS  PubMed  Google Scholar 

  22. DiSanto, J. P., Muller, W., Guy-Grand, D., Fischer, A., and Rajewsky, K. Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor gamma chain (1995) Proc Natl Acad Sci USA 92, 377–81.

    Article  CAS  PubMed  Google Scholar 

  23. Ohbo, K., Suda, T., Hashiyama, M., Mantani, A., Ikebe, M., Miyakawa, K., Moriyama, M., Nakamura, M., Katsuki, M., Takahashi, K., Yamamura, K., and Sugamura, K. Modulation of hematopoiesis in mice with a truncated mutant of the interleukin-2 receptor gamma chain (1996) Blood 87, 956–67.

    CAS  PubMed  Google Scholar 

  24. Blom, B., Spits, H., and Krimpenfort, P. The role of the common gamma chain of the IL-2, IL-4, IL-7 and IL15 receptors in the developmental of lymphocytes: constitutive expression of Bcl-2 does not rescue the development defects in gamma common-deficient mice (1996) in Cytokines and Growth Factors in Blood Transfusion, C.Th. Smit Sibinga, P.C. Das, B. Lowenberg (Eds.) Developments in hematology and immunology, Vol. 32, pp. 3–11, Kluwer Academic Publishers, Dordrecht, The Netherlands.

    Google Scholar 

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Legrand, N., Weijer, K., Spits, H. (2008). Experimental Model for the Study of the Human Immune System. In: Ewbank, J., Vivier, E. (eds) Innate Immunity. Methods in Molecular Biology™, vol 415. Humana Press. https://doi.org/10.1007/978-1-59745-570-1_4

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  • DOI: https://doi.org/10.1007/978-1-59745-570-1_4

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-746-4

  • Online ISBN: 978-1-59745-570-1

  • eBook Packages: Springer Protocols

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