Generation of primary antigen-specific human T- and B-cell responses in immunocompetent SCID-hu mice

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Histological analysis of human Sk-LN grafts of SCID-hu IC mice, 3 months after transplantation.
Figure 2: Histological analysis of human Sk-LN grafts of SCID-hu IC mice after immunization with TT.
Figure 3: Histological analysis of the B-cell populations in the Sk-LN grafts of SCID-hu IC mice after immunization with TT.
Figure 4: Antibody responses in SCID-hu IC mice.
Figure 5: TT-specific proliferation of T-cell lines isolated from the Sk-LN grafts of SCID-hu IC mice immunized with TT.

References

  1. 1

    Bosma, G.C., Custer, R.P. & Bosma, M.J. A severe combined immunodeficiency mutation in the mouse. Nature 301, 527– 530 (1983).

  2. 2

    Mosier, D.E., Gulizia, R.J., Baird, S.M. & Wilson, D.B. Transfer of a functional human immune system to mice with severe combined immunodeficiency. Nature 335, 256– 259 (1988).

  3. 3

    Kamel-Reid, S. & Dick, J.E. Engraftment of immune-deficient mice with human hematopoietic stem cells. Science 242, 1706–1709 (1988).

  4. 4

    McCune, J.M. et al. The SCID-hu mouse: Murine model for the analysis of human hematolymphoid differentiation and function. Science 241, 1632–1639 (1988).

  5. 5

    Namikawa, R., Weilbaecher, K.N., Kaneshima, H., Yee, E.J. & McCune, J.M. Long-term human hematopoiesis in the SCID-hu mouse. J. Exp. Med. 172, 1055 –1063 (1990).

  6. 6

    Greiner, D.L., Hesselton, R.A. & Shultz, L.D. SCID mouse models of human stem cell engraftment. Stem Cells 16, 166–177 ( 1998).

  7. 7

    Roncarolo, M.G., Carballido, J.M., Rouleau, M., Namikawa, R. & de Vries, J.E. Human T- and B-cell functions in SCID-hu mice. Semin. Immunol. 8, 207– 213 (1996).

  8. 8

    Kyoizumi, S. et al. Implantation and maintenance of functional human bone marrow in SCID-hu mice. Blood 79, 1704– 1711 (1992).

  9. 9

    Carballido, J.M. et al. IL-4 induces human B cell maturation and IgE synthesis in SCID-hu mice. Inhibition of ongoing IgE production by in vivo treatment with an IL-4/IL-13 receptor antagonist. J. Immunol. 155, 4162–4170 (1995).

  10. 10

    Stein, H., Gerdes, J. & Mason, D.Y. The normal and malignant germinal centre. Clin. Haematol. 11, 531–559 (1982).

  11. 11

    Steinman, R.M., Pack, M. & Inaba, K. Dendritic cells in the T-cell areas of lymphoid organs. Immunol, Rev. 156, 25–37 ( 1997).

  12. 12

    Krowka, J.F., Sarin, S., Namikawa, R., McCune, J.M. & Kaneshima, H. Human T cells in the SCID-hu mouse are phenotypically normal and functionally competent. J. Immunol. 146, 3751–3756 (1991).

  13. 13

    Fraser, C.C., Chen, B.P., Webb, S., van Rooijen, N. & Kraal, G. Circulation of human hematopoietic cells in severe combined immunodeficient mice after Cl2MDP-liposome-mediated macrophage depletion. Blood 86, 183–192 ( 1995).

  14. 14

    Mazingue, C., Cottrez, F., Auriault, C., Cesbron, J.Y. & Capron, A. Obtention of a human primary humoral response against schistosome protective antigens in severe combined immunodeficiency mice after the transfer of human peripheral blood mononuclear cells. Eur. J. Immunol. 21, 1763–1766 (1991).

  15. 15

    Duchosal, M.A. et al. Immunization of hu-PBL-SCID mice and the rescue of human monoclonal Fab fragments through combinatorial libraries. Nature 355, 258–262 (1992).

  16. 16

    Abedi, M.R., Christensson, B., Islam, K.B., Hammarstrom, L. & Smith, C.I. Immunoglobulin production in severe combined immunodeficient (SCID) mice reconstituted with human peripheral blood mononuclear cells. Eur. J. Immunol. 22, 823–828 (1992).

  17. 17

    Martensson, C., Kristensson, K., Kalliomaki, S., Borrebaeck, C.A. & Carlsson, R. Antigen-specific human immunoglobulin production in SCID mice transplanted with human peripheral lymphocytes is dependent on CD4+ CD45RO+ T cells. Immunology 83, 171–179 ( 1994).

  18. 18

    Sandhu, J., Shpitz, B., Gallinger, S. & Hozumi, N. Human primary immune response in SCID mice engrafted with human peripheral blood lymphocytes. J. Immunol. 152, 3806 –3813 (1994).

  19. 19

    Delhem, N. et al. Primary Th1 cell immunization against HIV gp160 in SCID-hu mice coengrafted with peripheral blood lymphocytes and skin. J. Immunol. 161, 2060–2069 (1998).

  20. 20

    Tary-Lehmann, M., Lehmann, P.V., Schols, D., Roncarolo, M.G. & Saxon, A. Anti-SCID mouse reactivity shapes the human CD4+ T cell repertoire in hu-PBL-SCID chimeras. J. Exp. Med. 180, 1817–1827 (1994).

  21. 21

    Murphy, W.J., Bennett, M., Anver, M.R., Baseler, M. & Longo, D.L. Human–mouse lymphoid chimeras: Host-vs.-graft and graft-vs.-host reactions. Eur. J. Immunol. 22, 1421–1427 (1992).

  22. 22

    Hoffmann- Fezer, G., Gall, C., Zengerle, U., Kranz, B. & Thierfelder, S. Immunohistology and immunocytology of human T-cell chimerism and graft-versus-host disease in SCID mice. Blood 81 , 3440–3448 (1993).

  23. 23

    Pflumio, F., Lapidot, T., Murdoch, B., Patterson, B. & Dick, J.E. Engraftment of human lymphoid cells into newborn SCID mice leads to graft-versus-host disease. Int. Immunol. 5, 1509–1522 (1993).

  24. 24

    Roncarolo, M.G. & Carballido, J.M. Construction of human-SCID chimeric mice. in Current Protocols in Immunology . (Coligan, J.E., Kruisbeek, A.M., Margulies, D.H., Shevach, E.M. & Strober, W. eds.) 4.8.1–4.8.17, (John Wiley, New York, 1998).

Download references

Acknowledgements

We thank I. Lindley, Novartis Research Institute, for critical reading of the manuscript. DNAX Research Institute of Molecular & Cellular Biology is supported by Schering-Plough Corporation.

Author information

Correspondence to José M. Carballido or Jan E. de Vries.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Carballido, J., Namikawa, R., Carballido-Perrig, N. et al. Generation of primary antigen-specific human T- and B-cell responses in immunocompetent SCID-hu mice. Nat Med 6, 103–106 (2000). https://doi.org/10.1038/71434

Download citation

Further reading