MECHANISMS OF TOLERANCE IN MURINE RADIATION BONE MARROW CHIMERAS

Authors:
  • HAHugh Auchincloss
    Hugh Auchincloss
  • DSDavid H. Sachs
    David H. Sachs
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Abstract
Allogeneic chimeras were prepared using lethally irradiated B6 hosts and untreated marrow from exsanguinated BALB/e donors. For about two months after reconstitution, chimeras had very weak antihost cellmediated lymphocytotoxicity (CML) reactivity and little third-party alloreactivity. During this time a cell population capable of suppressing CML reactivity against both host and third-party alloantigens (i.e., antigennonspecific) was demonstrated in chimera spleens by in vitro mixing experiments. The putative suppressor cells were Thy-1-negative and radiation-sensitive. Subsequently, mature chimeras showed host tolerance and strong third-party alloreactivity. At this point suppressor mechanisms could no longer be demonstrated. These data are consistent with a clonal elimination hypothesis in that they do not provide evidence to indicate that maintenance of specific immune tolerance is mediated by an active suppressor mechanism.