HOMING OF CR-51-LABELED HUMAN PERIPHERAL LYMPHOCYTES TO GRAVES THYROID-TISSUE XENOGRAFTED INTO SCID MICE

We have recently described a NUDE/SCID mouse model that has been usefu l for the study of human thyroid autoimmunity in in vivo conditions, T he reappearance of lymphocytic infiltration in Graves' thyroid tissue and a humoral response in SCID mice (rexenografted with normalized thy roid tissues from NUDE mice) was detected only if autologous Graves' h uman peripheral lymphocytes (PBMC) were engrafted into the same animal s, Therefore it was presumed that some autoreactive PBMC directed them selves to the thyroid, However, there was previously no direct evidenc e regarding the trafficking of the engrafted PBMC to the target tissue , To elucidate this point we have studied the migration of 51Cr-labele d PBMC in SCUD mice, Human thyroid tissue from six Graves' disease (GD ) patients and six patients with nontoxic nodular goiter were initiall y xenografted into NUDE mice for 8 weeks, The same tissues were retrie ved and rexenografted into several ''virgin'' SCID mice, i.e., no prev ious xenografts, Autologous PBMC were isolated from blood of the same patients obtained at the time of the tissue rexenograftment and labele d with radioactive Cr-51. Twenty million labeled PBMC were engrafted i nto each SCUD mouse, The distribution of labeled lymphocytes into mous e organs and trafficking into Graves' and normal xenografts was measur ed, A significant amount of radioactivity in Graves' xenografts was de tected after 1 week with the peak of radioactivity at 2-3 weeks, This radioactivity was significantly higher than radioactivity in surroundi ng tissues (skin, muscle), In contrast, homing of autologous lymphocyt es into normal paranodular thyroid tissue was very minimal; the radioa ctivity of GD thyroid xenografts with engrafted autologous lymphocytes was significantly higher than that of normal tissues, These results a lso parallel the histological picture, in which the normal tissues rem ained normal while lymphocytic infiltration reappeared in Graves' tiss ues, Distribution of labeled lymphocytes to the mouse organs, includin g the mouse thyroid, was not different between two groups, These findi ngs further support our hypothesis that Graves' PBMCs contain memory c ells that are committed to return to their autologous thyroid target a nd set up a gradually amplifying immune assault.