Advertisement

Is tolerance a prospective for clinical research?

  • John W. Fabre
Conference paper

Abstract

Tolerance is an emotive issue in transplantation. It is the promised land for which we all strive and which we all hope we shall live to see. In such circumstances, tolerance must always be a prospective for clinical research! The question is, therefore, better posed in a more optimistic fashion and with a small act of faith: do we, in 1991, have that crucial combination of basic scientific knowledge and creative imagination to make it possible?

Key words

Tolerance induction Non specific immunosuppression T cells 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Owen RD (1945) Immunogenetic consequence of vascular anastomoses between bovine twins. Science 102:400–401PubMedCrossRefGoogle Scholar
  2. 2.
    Lillie FR (1916) The theory of the freemartin state. Science 43: 611–613PubMedCrossRefGoogle Scholar
  3. 3.
    Burnet FM, Fenner F (1949) The production of antibodies, 2nd edn. Macmillan, p 76Google Scholar
  4. 4.
    Billingham RE, Brent L, Medawar PB (1953) Actively acquired tolerance of foreign cells. Nature 4379:603–606CrossRefGoogle Scholar
  5. 5.
    Marrack P, Lo D, Brinster R, Palmiter R, Burkly L, Flavell RH, Kapler J (1988) The effect of thymus environment on T cell development and tolerance. Cell 53:627–634PubMedCrossRefGoogle Scholar
  6. 6.
    Webb S, Morris C, Sprent J (1990) Extrathymic tolerance of mature T cells: clonal elimination as a consequence of immunity. Cell 63:1249–1256PubMedCrossRefGoogle Scholar
  7. 7.
    Mueller DL, Jenkins MK, Schwartz RH (1989) Clonal expansion versus functional clonal inactivation: a costimulatory signalling pathway determines the outcome of T cell antigen receptor occupancy. Annu Rev Immunol 7:445–480PubMedCrossRefGoogle Scholar
  8. 8.
    Ramsdell F, Lantz T, Fowlkes BJ (1989) A nondeletional mechanism of thymic self tolerance. Science 246:1038–1041PubMedCrossRefGoogle Scholar
  9. 9.
    Batchelor JR, Lombardi G, Lechler RI (1989) Speculations on the specificity of suppression. Immunol Today 10:37–40PubMedCrossRefGoogle Scholar
  10. 10.
    Nikolic-Zugic J (1991) Phenotypic and functional stages in the intrathymic development of ccpT cells. Immunol Today 12: 65–69PubMedCrossRefGoogle Scholar
  11. 11.
    Hunig T, Tiefenthaler G, Lawetzky A, Kubo R, Schlipkoter E (1989) T-cell subpopulations expressing distinct forms of the TCR in normal, athymic and neonatally TCR αβ-suppressed rats. Cold Spring Harbour Symposia on Quantitative Biology 54: 61–68CrossRefGoogle Scholar
  12. 12.
    Barclay AN, Mayohoffer G (1981) Bone marrow origin of la positive cells in the medullar of rat thymus. J Exp Med 153: 1666–1671PubMedCrossRefGoogle Scholar
  13. 13.
    Monaco P, Wood ML (1970) Studies on heterologous antilym-phocyte serum in mice. VII. Optimal cellular antigen for induction of immunologic tolerance with antilymphocyte serum. Transplant Proc 2:489–496PubMedGoogle Scholar
  14. 14.
    Barber WH, Laskow DA, Deierhoi MH, Juilian BA, Curtis JJ, Diethelm AG (1989) Use of cryopreserved donor bone marrow in cadover kidney allograft recipient. Transplant Proc 21:1787–1789PubMedGoogle Scholar
  15. 15.
    Berzofksy JA, Brett SJ, Streicher GZ, Takahashi H (1988) Antigen processing for presentation of T lymphocytes: function, mechanisms and implications for the T-cell repertoire. Immunol Rev 106:5–31CrossRefGoogle Scholar
  16. 16.
    Bevan MJ (1984) High determinant density may explain the phenomenon of alloreactivity. Immunol Today 5:128–131CrossRefGoogle Scholar
  17. 17.
    Butcher GW, Howard JC (1982) Genetic control of transplant rejection. Transplantation 34:161–166PubMedCrossRefGoogle Scholar
  18. 18.
    Lechler RI, Batchelor JR (1982) Restoration of immunogenicity to passenger cell-depleted kidney allografts by the addition of donor strain dendritic cells. J Exp Med 155:31–41PubMedCrossRefGoogle Scholar
  19. 19.
    Sherwood RA, Brent L, Rayfield LS (1986) Presentation of al-loantigens by host cells. Eur J Immunol 16:569–574PubMedCrossRefGoogle Scholar
  20. 20.
    Fangmann J, Dalchau R, Fabre JW. The rejection of skin allografts by indirect recognition of donor class I MHC peptides. J Exp Med (Submitted)Google Scholar
  21. 21.
    Dalchau R, Fangmann J, Fabre JW. Allorecognition of isolated denatured chains of class I and class II MHC molecules. Eur J Immunol (In Press)Google Scholar
  22. 22.
    Murphy KM, Heimberger AB, Loh DY (1990) Induction by antigen of intrathymic apotosis of CD4+, CD8 +, TCR10 thymocytes in vivo. Science 250:1720–1723PubMedCrossRefGoogle Scholar
  23. 23.
    Steinman RM, Witman MD (1978) Lymphoid dendritic cells are potent stimulators of the primary mixed leucocyte reaction in mice. Proc Natl Acad Sci USA 75:5132–5136PubMedCrossRefGoogle Scholar
  24. 24.
    Halttunen J (1990) Failure of rat kidney nephron components to induce allogeneic lymphocytes to proliferate in mixed lymphocyte kidney cell culture. Transplantation 50:481–487PubMedCrossRefGoogle Scholar
  25. 25.
    Hart DNJ, Fabre JW (1981) Demonstration and characterization of la positive dendritic cells in the interstitial connective tissues of rat heart and other tissues, but not brain. J Exp Med 154:347–361PubMedCrossRefGoogle Scholar
  26. 26.
    Milton AD, Spencer SC, Fabre JW (1986) The effects of cyclosporin A on the induction of donor class I and class II MHC antigens in heart and kidney allografts in the rat. Transplantation 42: 337–347PubMedCrossRefGoogle Scholar
  27. 27.
    Hart DNJ, Fabre JW (1981) Localisation of MHC antigens in long-surviving rat renal allografts: probable implication of the passenger leucocyte in graft adaptation. Transplant Proc 13:95–99PubMedGoogle Scholar
  28. 28.
    Fabre JW (1982) The rat kidney allograft model: was it all too good to be true? Transplantation 34:223–224PubMedCrossRefGoogle Scholar
  29. 29.
    Slavin S (1987) Total lymphoid irradiation. Immunol Today 3: 88–92CrossRefGoogle Scholar
  30. 30.
    Hart DNJ, Fabre JW (1982) The mechanism of induction of passive enhancement: evidence for an interaction of enhancing antibody with donor interstitial dendritic cells. Transplantation 33:319–322PubMedCrossRefGoogle Scholar
  31. 31.
    French ME, Batchelor JR (1972) Enhancement of renal allograft in rats and man. Transplant Rev 13:115–141PubMedGoogle Scholar
  32. 32.
    Fabre JW (1982) Specific immunosuppression. In: PJ Morris (ed) Tissue Transplantation, Clinical Surgery International, vol.8. Churchill Livingstone, Edinburgh, pp 80–94Google Scholar
  33. 33.
    MacDonald HR, Hengartner H, Pedrazzini T (1988) Intra-thymic deletion of self-reactive cells prevented by neonatal anti-CD4 antibody treatment. Nature 335:174–176PubMedCrossRefGoogle Scholar
  34. 34.
    Medawar PB (1963) The use of antigenic tissue extracts to weaken the immune reaction against skin homografts in mice. Transplantation 1:21–38PubMedCrossRefGoogle Scholar
  35. 35.
    Reisfeld RA, Kahan BD (1971) Extraction and purification of soluble histocompatibility antigens. Transplant Rev 6:81–112PubMedGoogle Scholar
  36. 36.
    Priestley CA, Dalchau R, Sawyer GJ, Fabre JW (1989) A detailed analysis of the potential of water soluble classical class I MHC molecules for the suppression of kidney allograft rejection and in vitro cytotoxic T cell responses. Transplantation 48:1031–1038PubMedCrossRefGoogle Scholar
  37. 37.
    Salaun J, Bandeira A, Khazaal I, Caiman F, Coltbey M, Coutinho A, Le Douarin NM (1990) Thymic epithelium tolerizes for histocompatibility antigens. Science 247:1471–1474PubMedCrossRefGoogle Scholar
  38. 38.
    Cobbold SP, Martin G, Waldmann H (1990) The induction of skin graft tolerance in MHC mismatched or primed recipients: primed T cells can be tolerised in the periphery with anti CD4 and anti CD8 antibodies. Eur J Immunol 20:2747–2755PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1992

Authors and Affiliations

  • John W. Fabre
    • 1
  1. 1.Division of Cell and Molecular BiologyThe Institute of Child HealthLondonUK

Personalised recommendations