Letter | Published:

T-cell-derived helper factor allows in vivo induction of cytotoxic T cells in nu/nu mice

Abstract

T-cell immunocompetence and diversity are thought to be generated in the thymus1,2. This view is based on the findings that (1) T-cell ontogeny is thymus dependent3,4, (2) the major histocompatibility restrictions of T-cell interactions are phenotypically related to the H–2 type of the thymus5–9, and (3) the phenotypic manifestation of H–2-linked immune responsiveness parallels the restriction elements selected in thymus10–12. However, it is unclear whether pre-thymic cells programmed to develop into T cells do already express a receptor diversity, also whether pre-thymic cells have the potential to react against self-antigens, and whether the mechanism of self-tolerance is initiated in the thymus by either elimination or suppression of self-reactive clones. If it were possible to confer on pre-thymic cells antigen-specific effector functions, the impact of the thymus on the generation of T-cell diversity and function could be analysed in more detail. In mice, the nude mutation lacks a functioning thymus13,14; nu/nu mice possess a thymic rudiment which is epithelial in the embryo15 and a fibrous, cystic remnant in adult15,16; this remnant is not populated by lymphoid cells15–17. At present, the absence of immunocompetent T cells in nu/nu mice is explained by a lack of thymic differentiation and maturation of pre-thymic cells (reviewed in ref. 13). Here we report that injection of allogeneic stimulator cells plus a Lyt 1 T-cell-derived helper factor18,19, termed interleukin 2 (for the system of nomenclature, see ref. 20) allows lymphocytes of nu/nu mice to differentiate in vivo into alloreactive cytotoxic T lymphocytes (CTLs).

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

    Burnet, F. M. Immunological Surveillance (Pergamon, Sydney, 1970).

  2. 2

    Jerne, N. K. Eur. J. Immun. 1, 1–9 (1971).

  3. 3

    Miller, J. F. A. P. & Osoba, D. Physiol. Rev. 47, 437–478 (1967).

  4. 4

    Davies, A. J. S., Lenchars, E., Wallis, V., Marchant, R. & Elliot, E. V. Transplantation 5, 222–231 (1967).

  5. 5

    Doherty, P. C., Blanden, R. V. & Zinkernagel, R. M. Transplant. Rev. 29, 89–124 (1976).

  6. 6

    Zinkernagel, R. M. et al. J. exp. Med. 147, 822–896 (1978).

  7. 7

    Bevan, M. J. Nature 269, 417–418 (1978).

  8. 8

    Pfizenmaier, K., Starzinski-Powitz, A., Rodt, H., Röllinghoff, M. & Wagner, H. J. exp. Med. 143, 999–1004 (1976).

  9. 9

    Gordon, R. D., Simpson, E. & Samelson, L. E. J. exp. Med. 142, 1108–1120 (1975).

  10. 10

    v. Boehmer, H., Haas, W. & Jerne, N. K. Proc. natn. Acad. Sci. U.S.A. 75, 2439–2441 (1978).

  11. 11

    Matsunaga, T. & Simpson, E. Proc. natn. Acad. Sci. U.S.A. 75, 6207–6209 (1978).

  12. 12

    Zinkernagel, R. M., Althage, A., Cooper, S., Callahan, G. N. & Klein, J. J. exp. Med. 148, 805–810 (1978).

  13. 13

    Kindred, B. Prog. Allergy 26, 137–238 (1979).

  14. 14

    Pantelouris, E. M. Nature 217, 370–371 (1968).

  15. 15

    Jordan, R. K., Owen, J. J. T. & Raff, M. C. Eur. J. Immun. 7, 736–743 (1977).

  16. 16

    Owen, J. J. T., Jordan, R. F. & Raff, M. C. Eur. J. Immun. 5, 653–656 (1975).

  17. 17

    Cordier, A. C. J. ultrastruct. Res. 47, 26–32 (1974).

  18. 18

    Wagner, H. & Röllinghoff, M. J. exp. Med. 148, 1523–1528 (1977).

  19. 19

    Watson, J., Gillis, St., Marbrook, J., Mochizuki, D. & Smith, K. A. J. exp. Med. 150, 849–861 (1979).

  20. 20

    2nd Int. Workshop, Ermatingen (1979).

  21. 21

    Wagner, H., Röllinghoff, M., Schawaller, R., Hardt, C. & Pfizenmaier, K. Nature 280, 5721–5722 (1979).

  22. 22

    Irlé, C., Piguet, P. F. & Vasalli, P. J. exp. Med. 148, 32–45 (1978).

  23. 23

    Wagner, H., Röllinghoff, M., Pfizenmaier, K., Hardt, C. & Johnscher, G. J. Immun. (in the press).

  24. 24

    Piguet, P. F. & Vasalli, P. J. Immun. 120, 79–83 (1978).

  25. 25

    Loor, F., Amstutz, H., Hägg, L. B., Major, K. S. & Rochants, G. E. Eur. J. Immun. 6, 663–667 (1976).

  26. 26

    Hair, J. in Proc. 1st Int. Workshop in Nude Mice, 23 (Fischer, Stuttgart, 1974).

  27. 27

    Feldman, M., Wagner, H., Basten, A. & Holmes, M. Aust. J. exp. Biol. med. Sci. 50, 651–660 (1972).

  28. 28

    Wagner, H. J. Immun. 109, 630–635 (1972).

  29. 29

    Komuro, K. & Boyse, E. A. J. exp. Med. 138, 479–483 (1973).

  30. 30

    Scheid, M. P., Golstein, G. & Boyse, E. A. Science 190, 2111–2112 (1974).

  31. 31

    Sato, V. L., Waksal, S. D. & Herzenberg, L. A. Cell. Immun. 24, 173–179 (1976).

  32. 32

    Milewicz, C., Miller, H. G. & Esselman, W. J. J. Immun. 117, 1774–1779 (1976).

  33. 33

    Scheid, M. P. et al. J. exp. Med. 138, 1027–1031 (1973).

  34. 34

    Gillis, St., Union, N. A., Baker, P. E. & Smith, K. A. J. exp. Med. 149, 1460–1476 (1979).

  35. 35

    Bevan, M. J. Proc. natn. Acad. Sci. U.S.A. 74, 2094–2098 (1977).

  36. 36

    Finberg, R., Burakoff, St., Cantor, H. & Benacerraf, B. Proc. natn. Acad. Sci. U.S.A. 75, 5145–5149 (1978).

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

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.