Graves' disease / model of SCID mouse

Summary

The severe combined immunodeficient (SCID) mouse constitutes an interesting but not ideal model for the study of human Graves' disease (GD) thyroid tissue. While certainly thyroid tissue survives in the SCID mouse, the lymphocytes do not seem to be able to exert their effects in a long term manner as they do in the human host. Primary thyroid xenografts of GD will not remain hyperfunctional, and antibodies seem to subside after several weeks. GD thyroid tissue which has been removed from its immune environment by passing it through the nude mouse for eight weeks, and then re-xenografted in the SCID mouse, will again manifest lymphocytic infiltration only upon injection of autologous human peripheral blood mononuclear cells which thus reconstitute the lesion to some degree. However, we have not been able to reproduce GD by this procedure. We have been able to show organ-specific homing of the autologous peripheral blood lymphocytes to the GD thyroid tissue and a reappearance of histological lymphocytic infiltration, thyrocyte HLA-DR and ICAM-1 expression, and the reappearance of circulating thyroid autoantibodies after injection of autologous peripheral blood mononuclear cells (PBMC). (No such changes occur when normal thyroid tissue is similarly studied). This can be greatly magnified by deleting the CD8 cells prior to (PBMC) injection and can be prevented by adding a surfeit of CD8 cells instead, signifying that this subpopulation of lymphocytes contains suppressor T lymphocytes. The model affords means of studying various immunomodulators in an in vivo situation. Attempts are being made in various centres to more closely simulate GD but it may be necessary to have other mouse models with fewer natural killer (NK) cells to be able to successfully maintain the lymphocytes and tissue in its original state.