Regulation of Thymic Development by Neprilysin Inhibition

  • Sandrine Guérin
  • Patrick Auberger
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 421)

Abstract

Development of T lymphocyte is regulated by both thymocyte-stromal cell interactions and production of soluble factors such as cytokines, peptides and hormones. The local concentration of active biological peptides is regulated by a specialized family of enzymes expressed at the cell surface, the ectopeptidases. We found that treatment of fetal thymic organ cultures (FTOC) with the specific CD10 (endopeptidase 24.11) inhibitor, (N-(3-[(hydroaxyamino)carbonyl]-2-benzylidene-1-oxopropyl]-N-glycine), RB25 results in a marked delay in thymocyte differentiation. RB25 causes a significant decrease in the number of DP (CD4+CD8+) cells in favor of the TN (TcRαβCD4CD8) population. RB25 also blocks T lymphocyte differentiation in FTOC when preinjected into pregnant mice. Finally, RB25 was found to essentially affect the CD44+CD25 and CD44CD25 thymocytes in “in vitro” and “in vivo” experiments after 2 days FTOC. Thus, a selective and stable endopeptidase 24.11 inhibitor impairs T cell development, an observation in agreement with the involvement of the CD10 antigen in early T cell development.

Keywords

Pregnant Mouse Thymic Epithelial Cell Lymphocyte Differentiation Cell Surface Staining Thymic Development 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Shipp, M. A., Vijayaraghavan, J., Schmidt, E. V., Masteller, E. L., D’Adamio, L., Hersh, L. B. & Reinherz, E. L. (1989). Proc. Natl. Acad. Sci. USA 86, 297–301Google Scholar
  2. 2.
    Xu, D., Emoto, N., Giaid, A., Slaughter, C., Kaw. S., deWitt, D. & Yanagisawa, M. (1994). Cell 78, 473–485PubMedCrossRefGoogle Scholar
  3. 3.
    Shipp, M. & Look, T. (1993). Blood 82. 1052–1070PubMedGoogle Scholar
  4. 4.
    Roques, B. P., Noble, F., Daugé, V., Fournié-Zaluski, M. C. & Beaumont, A. (1993). Pharmacol. Rev. 45, 87–146PubMedGoogle Scholar
  5. 5.
    Erdös, E. & Skidgel, R. (1989). FASEB. J. 3, 145–151PubMedGoogle Scholar
  6. 6.
    Salles, G., Rodewald, H.-R., Chin, B., Reinherz, E.-L. & Shipp, M.-A. (1993) I. Proc. Natl. Acad. Sci. USA 90, 7618–7622CrossRefGoogle Scholar
  7. 7.
    Salles, G., Chen, C. Y., Reinherz, E. L. & Shipp, M. A. (1992) Blood 80, 2021–2029PubMedGoogle Scholar
  8. 8.
    Mari, B., Breittmayer, J.-P., Guérin, S., Belhacène, N., Peyron, J.-F., Decken, M., Rossi, B. & Auberger, P. (1994), Immunology 82, 833–838Google Scholar
  9. 9.
    Guérin, S., Mari, B., Belhacène, N., Rossi, B. & Auberger, P. (Cell. Immunol.in press)Google Scholar
  10. 10.
    Small, M., Kaiser, M., Tse, W., Heimfeld, S. & Blumberg, S. (1996). Eur. J. Immunol. 26, 961–964PubMedCrossRefGoogle Scholar
  11. 11.
    Mari, B., Checler, F., Ponzio, G., Peyron, J.-F., Manié, S., Farahi Far, D., Rossi, B. & Auberger, P. (1992). EMBO. J. 11, 3875–3885PubMedGoogle Scholar
  12. 12.
    Hernandez, J., Soleilhac, J., Roques, B. & Fournié-Zaluski, M. (1988) J. Med. Chem. 31, 1825–1831PubMedCrossRefGoogle Scholar
  13. 13.
    Godfrey, D., Kennedy, J., Suda, T. & Zlotnik, A. (1993). J. lmmunol. 150, 4244–4252Google Scholar
  14. 14.
    Dardenne, M. & Savino, W. (1994). Immune’. Today 15, 518–551CrossRefGoogle Scholar
  15. 15.
    Lalli, E.. Sassone-Corsi, P. & Ceredig, R. (1995) EMBOJ. 15, 52S - 537Google Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Sandrine Guérin
    • 1
  • Patrick Auberger
    • 1
  1. 1.Faculté de MédecineCJF INSERM 9605Nice cédex 02France

Personalised recommendations