Phenotypic differences between αβ versus β T-cell receptor transgenic mice undergoing negative selection

Abstract

T-CELL differentiation in the thymus is thought to involve a progression from the CD4CD8 phenotype through CD4+CD8+ intermediates to mature CD4+ or CD8+ cells1-3. There is evidence that during this process T cells bearing receptors potentially reactive to 'self are deleted by a process termed 'negative selection'4-10. One example of this process occurs in mice carrying polymorphic Mis antigens, against which a detectable proportion of T cells are autoreactive. These mice show clonal deletion of thymic and peripheral T-cell subsets that express the autoreactive Vβ3 segment of the T-cell antigen receptor, but at most a two-fold depletion of thymic cells at the CD4+CD8+ stage5-7. By contrast, transgenic mice bearing both α and β chain genes encoding autoreactive receptors recognizing other ligands, show severe depletion of CD4+CD8+ thymocytes as well8,9, suggesting that negative selection occurs much earlier. We report here the Mis 2a/3a mediated elimination of T cells expressing a transgene encoded Vβ3-segment, in T-cell receptor α/β and β-transgenic mice. Severe depletion of CD4+CD8+ thymocytes is seen only in the α/β chain transgenic mice, whereas both strains delete mature Vβ3 bearing CD4+ and CD8+ T cells efficiently. We conclude that severe CD4+CD8 thymocyte deletion in α/β transgenic mice results from the premature expression of both receptor chains, and does not reflect a difference in the timing or mechanism of negative selection for Mis antigens5-7 as against the allo- and MHC class 1-restricted antigens used in the other studies8-9.

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

    Guidos, C. et al. Proc. natn. Acad. Sci. U.S.A. (in the press).

  2. 2

    Fowlkes, B. J., Edison, L., Mathieson, B. J. & Chused, T. M. J. exp. Med 162, 802–822 (1985).

  3. 3

    Smith, L. Nature 326, 798–800 (1987).

  4. 4

    Kappler, J. W. et al. Cell 49, 263–271 (1987).

  5. 5

    Kappler, J., Staerz, U., White, J. & Marrack, P. Nature 332, 35–40 (1988).

  6. 6

    MacDonald, H. R. et al. Nature 332, 40–45 (1988).

  7. 7

    Pullen, A. M., Marrack, P. & Kappler, J. W. Nature 335, 796–801 (1988).

  8. 8

    Kisielow, P., Bluthmann, H., Staerz, U. D., Steinmetz, M. & von Boehmer, H. Nature 333, 742–746 (1988).

  9. 9

    Sha, W. C. et al. Nature 336, 73–76 (1988).

  10. 10

    Pircher, H. et al. EMBO J. 8, 719–727 (1989).

  11. 11

    Ivars, F. et al. in The T Cell Receptors (eds Davis, M. M. & Kappler. J.) 184–197 (Liss, New York, 1987).

  12. 12

    Berg, L. J. et al. Molec. cell Biol. 8, 5459–5469 (1988).

  13. 13

    Berg, L. J. et al. Cell (in the press).

  14. 14

    Hedrick, S. M. et al. Cell 30, 141–152 (1982).

  15. 15

    Abe, R., Vacchio, M. S., Fox, B. & Hodes, R. J. Nature 335, 827–830 (1988).

  16. 16

    Fry, A. M. & Matis, L. A. Nature 335, 830–832 (1988).

  17. 17

    Pullen, A. M., Marrack, P. & Kappler, J. W. J. Immun. 142, 3033–3037 (1989).

  18. 18

    White, J. et al. Cell 56, 27–35 (1989).

  19. 19

    McDuffie, M., Born, W., Marrack, P. & Kappler, J. W. Proc. natn. Acad. Sci. U.S.A. 83, 8728–8732 (1986).

  20. 20

    Fowlkes, B. J., Schwartz, R. H. & Pardoll, D. M. Nature 334, 620–623 (1988).

  21. 21

    MacDonald, H. R., Hengartner, H. & Pedrazzini, T. Nature 335, 174–176 (1988).

  22. 22

    Finkel, T. H., Marrack, P., Kappler, J. W., Kubo, R. T. & Cambier, J. C. J. Immun. 142, 3006–3012 (1989).

  23. 23

    Kappler, J., Roehm, N. & Marrack, P. Cell 49, 273–280 (1987).

  24. 24

    Dialynas, D. P. J. Immun. 131, 2445–2451 (1984).

  25. 25

    Ledbetter, J. A. & Herzenberg, L. A. Immunol. Rev. 47, 63–90 (1979).

  26. 26

    Hayakawa, K., Hardy, R. R., Parks, D. R., Herzenberg, L. A. & Herzenberg, L. A., J. exp. Med. 157, 202–218 (1983).

  27. 27

    Havran, W. L. et al. Nature 330, 170–173 (1987).

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.