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Mixed Chimerism and Transplantation Tolerance

  • D. H. Sachs
  • Y. Sharabi
  • M. Sykes

Abstract

Reconstitution of lethally irradiated mice with MHC mismatched allogeneic bone marrow leads to allogeneic reconstitution and specific tolerance. Such reconstitution does not, however, provide a workable approach to achieving transplant tolerance for two reasons: 1) if mature T cells are not removed from the allogeneic inoculum, graft-versus-host disease (GVHD) ensues, and can be lethal; and 2) if mature T cells are removed from the allogeneic bone marrow inoculum the animals engraft allogeneically but are relatively immunoincompetent when examined late after reconstitution (Zinkernagel 1980). This immunoincompetence is presumably due to a failure of the newly maturing T cells in such animals to find appropriate presenting cells capable of presenting foreign antigens in the context of thymic MHC products. The new T cells develop in a host thymus, but the presenting cells, like the T cells, are derived from the allogeneic donor. Singer and colleagues (1981) have shown that mature T cells from such animals are in fact competent in vitro if allowed to react with antigen-presenting cells of appropriate host MHC type. Consistent with this finding, they showed, and we have confirmed (Ildstad 1985), that the reconstitution of such animals with a mixture of T-cell-depleted host and donor bone marrow cells leads to survival of both lymphohematopoietic lineages, and spleen cells from such animals are immunocompetent (Fig. 1) and specifically unresponsive in vitro to both donor and host MHC.

Keywords

Total Body Irradiation Allogeneic Bone Marrow Natural Suppressor Donor Bone Marrow Cell Thymic Stroma 
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.

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References

  1. Batchelor JR, Phillips BE, Grennan D (1984) Transplantation. 37:43–46PubMedCrossRefGoogle Scholar
  2. Cobbold SP, Martin G, Qin S, Waldmann H (1986) Nature 323:164–166PubMedCrossRefGoogle Scholar
  3. Dorsch S, Roser B (1982) Transplantation 33:525–529PubMedCrossRefGoogle Scholar
  4. Holda JH, Maier T, Claman HN (1985) Immunol Rev 88:87–105PubMedCrossRefGoogle Scholar
  5. Ildstad ST, Wren SM, Bluestone JA, Barbieri SA, Sachs DH (1985) J Exp Med 162:231–244PubMedCrossRefGoogle Scholar
  6. Ildstad ST, Sachs DH (1984) Nature 307:168–170PubMedCrossRefGoogle Scholar
  7. Ildstad ST, Wren SM, Bluestone JA, Barbieri SA, Stephany D, Sachs DH (1986) J Immunol 136:28–33PubMedGoogle Scholar
  8. Sharabi Y, Sachs DH (1989) J Exp Med 169:493–502PubMedCrossRefGoogle Scholar
  9. Singer A, Hathcock KS, Hodes RJ (1981) J Exp Med 153:1286–1301PubMedCentralPubMedCrossRefGoogle Scholar
  10. Sprent J, Lo D, Gao EK, Ron Y (1988) Immunol Rev 101:173–90PubMedCrossRefGoogle Scholar
  11. Sykes M, Eisenthal A, Sachs DH (1988) J Immunol 140:2903–2911PubMedGoogle Scholar
  12. Sykes M, Sheard MA, Sachs DH (1988) J Exp Med 168:661–673PubMedCrossRefGoogle Scholar
  13. Zinkernagel RM, Althage A, Callahan G, Welsh, RM (1980) J Immunol 124:2356–2365PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • D. H. Sachs
  • Y. Sharabi
  • M. Sykes

There are no affiliations available

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