| Popis: |
A murine model of peripheral immunological tolerance has been studied. The data strongly support the view that the immunotolerance is induced as a consequence of exposure to a marker that pre-exists on the surfaces of splenic cells and thymic cells. Bone marrow cells as well as lymph node cells are incapable of inducing the tolerance. The spleen cells need not replicate or synthesize protein to induce the tolerance. When the surfaces of splenic cells are coupled with a hapten such a picryl chloride (TNP), the cells are no longer capable of inducing the tolerance. The data suggest local uptake and disintegration of FITC-labeled cells occurs at the subcutaneous injection site. The data also strongly support the view that suppressor cells induced among lymph node cells by the splenic marker were responsible for mediating the down-regulation of CTL development. Down-regulation appeared to emanate from suppressor cells. To become detectable, the suppression had to be triggered by re-exposure to syngeneic splenic cells that were hapten-coupled or not. However, the Ts cells (previously identified as CD8+) were not triggered by syngeneic lymph node cells or by allogeneic spleen cells. Once triggered, the suppression was manifested toward CTL generation agai nst hapten-coupled syngeneic antigens on either spleen or lymph node cells, but not against allogeneic antigens. Thus, the specificity of the tolerance was for altererd-self antigens despite its induction by unaltered spleen antigen. Furthermore, for suppression to be seen, the spleen antigen was not required to be on the hapten-coupled syngeneic cells used for the CTL immunization.The hypothesis is that deposition of self splenic cells subcutaneously in a lymph node environment activates a down-regulatory system that prevents initiation of immune responses to altered-self antigens. The regulation is mediated by T cells that are CD8+. The control system may be naturally existing and is triggered when the host is confronted with tissue damage, self antigens that are altered, or self antigens such as the splenic antigen in an unnatural setting. Immune reactions to foreign antigens remain intact. Such a system would have obvious survival value for the host. (Abstract shortened with permission of author.) |
