Letter | Published:

Development and function of T cells in mice rendered interleukin-2 deficient by gene targeting

Naturevolume 352pages621624 (1991) | Download Citation

Subjects

Abstract

INTERLEUKIN-2 (IL-2) is a lymphocytotropic hormone which is thought to have a key role in the immune response of mammalian cells. It is produced by a subpopulation of activated T-lymphocytes and acts in vitro as the principal auto- and paracrine T-cell growth factor (for reviews see refs 1–3). IL-2 is, however, not the sole T-cell growth factor4,5, nor does it act exclusively on T cells, also promoting growth of NK cells6 and differentiation of B cells7. A role for IL-2 in T-cell development has been postulated but remains controversial8–12. Here we test the requirement for IL-2 in vivo using IL-2-deficient mice generated by targeted recombination. We find that mice homozygous for the IL-2 gene mutation are normal with regard to thymocyte and peripheral T-cell subset composition, but that a dysregulation of the immune system is manifested by reduced polyclonal in vitro T-cell responses and by dramatic changes in the isotype levels of serum immunoglobulins.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Smith, K. A. Science 240, 1169–1176 (1988).

  2. 2

    Paul, W. E. Cell 57, 521–524 (1989).

  3. 3

    Mosmann, T. R. et al. Prog. Immun. 7, 611–618 (1989).

  4. 4

    Lee, F. et al. Proc. natn. Acad. Sci. U.S.A. 83, 2061–2065 (1986).

  5. 5

    Chazen, G. D., Pereira, G. M. B., LeGros, G., Gillis, S. & Shevach, E. M. Proc. Natn. Acad. Sci. U.S.A. 86, 5923–5927 (1989).

  6. 6

    Trinchieri, G. et al. J. exp. Med. 160, 1147–1169 (1984).

  7. 7

    Tigges, M. A., Casey, L. S. & Koshland, M. E. Science 243, 781–786 (1989).

  8. 8

    Takacs, L., Osawa, H. & Diamantstein, T. Eur. J. Immun. 14, 1152–1156 (1984).

  9. 9

    Jenkinson, E. J., Kingston, R. & Owen, J. J. T. Nature 329, 160–162 (1987).

  10. 10

    Tentori, L., Longo, D. L., Zuniga-Pflucker, J. C., Wing, C. & Kruisbeek, A. M. J. exp. Med. 168, 1741–1747 (1988).

  11. 11

    Plum, J. & de Smedt, M. Eur. J. Immun. 18, 795–799 (1988).

  12. 12

    MacDonald, H. R. et al. Immunol. Rev. 104, 157–182 (1988).

  13. 13

    Doetschman, T. et al. Nature 330, 576–578 (1987).

  14. 14

    Thomas, K. R. & Capecchi, M. R. Cell 51, 503–512 (1987).

  15. 15

    Thompson, S., Clarke, A. R., Pow, A. M., Hooper, M. L. & Melton, D. W. Cell 56, 313–321 (1989).

  16. 16

    Zijlstra, M., Li, E., Sajjadi, F., Subramani, S. & Jaenisch, R. Nature 342, 435–438 (1989).

  17. 17

    Fuse, A. et al. Nucleic Acids Res. 12, 9323–9331 (1984).

  18. 18

    Zurawski, S. M. & Zurawski, G. EMBO J. 7, 1061–1069 (1988).

  19. 19

    Evans, M. J. & Kaufman, M. H. Nature 292, 154–156 (1981).

  20. 20

    Shortman, K., Egerton, M., Spangrude, G. J. & Scollay, R. Semin. Immun. 2, 3–12 (1990).

  21. 21

    von Boehmer, H. & Kisielow, P. Science 248, 1369–1372 (1990).

  22. 22

    Weinberg, K. & Parkman, R. New Engl. J. Med. 322, 1718–1723 (1990).

  23. 23

    Chen-Bettecken, U., Wecker, E. & Schimpl, A. Proc. natn. Acad. Sci. U.S.A. 82, 7384–7388 (1985).

  24. 24

    Pahwa, R. et al. Proc. natn. Acad. Sci U.S.A. 86, 5069–5073 (1989).

  25. 25

    Hooper, M. et al. Nature 326, 292–295 (1987).

  26. 26

    Smith, A. G. & Hooper, M. L. Devl. Biol. 121, 1–9 (1987).

  27. 27

    Williams, R. L. et al. Nature 336, 684–687 (1988).

  28. 28

    Kubo, R., Born, W., Kappler, J., Marrack, P. & Pigeon, M. J. Immun. 142, 2736–2742 (1989).

  29. 29

    Molinaro, G. A., Maron, E., Eby, W. C. & Dray, S. Eur. J. Immun. 5, 771–774 (1975).

Download references

Author information

Affiliations

  1. Institute of Virology and Immunobiology, University of Würzburg, Versbacherstrasse 7, 8700, Würzburg, Germany

    • Hubert Schorle
    • , Thomas Holtschke
    • , Thomas Hünig
    • , Anneliese Schimpl
    •  & Ivan Horak

Authors

  1. Search for Hubert Schorle in:

  2. Search for Thomas Holtschke in:

  3. Search for Thomas Hünig in:

  4. Search for Anneliese Schimpl in:

  5. Search for Ivan Horak in:

About this article

Publication history

Received

Accepted

Issue Date

DOI

https://doi.org/10.1038/352621a0

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.