Homing of ⁵¹Cr-labeled human peripheral lymphocytes to Graves' thyroid tissue xenografted into SCID mice

We have recently described a NUDE/SCID mouse model that has been useful for the study of human thyroid autoimmunity in in vivo conditions. The reappearance of lymphocytic infiltration in Graves' thyroid tissue and a humoral response in SCID mice (rexenografted with normalized thyroid tissues from NUDE mice) was detected only if autologous Graves' human peripheral lymphocytes (PBMC) were engrafted into the same animals. Therefore it was presumed that some autoreactive PBMC directed themselves to the thyroid. However, there was previously no direct evidence regarding the trafficking of the engrafted PBMC to the target tissue. To elucidate this point we have studied the migration of ⁵¹Cr-labeled PBMC in SCID mice. Human thyroid tissue from six Graves' disease (GD) patients and six patients with nontoxic nodular goiter were initially xenografted into NUDE mice for 8 weeks. The same tissues were retrieved and rexenografted into several 'virgin' SCID mice, i.e., no previous xenografts. Autologous PBMC were isolated from blood of the same patients obtained at the time of the tissue rexenograftment and labeled with radioactive ⁵¹Cr. Twenty million labeled PBMC were engrafted into each SCID mouse. The distribution of labeled lymphocytes into mouse organs and trafficking into Graves' and normal xenografts was measured. A significant amount of radioactivity in Graves' xenografts was detected after 1 week with the peak of radioactivity at 2-3 weeks. This radioactivity was significantly higher than radioactivity in surrounding tissues (skin, muscle). In contrast, homing of autologous lymphocytes into normal paranodular thyroid tissue was very minimal; the radioactivity of GD thyroid xenografts with engrafted autologous lymphocytes was significantly higher than that of normal tissues. These results also parallel the histological picture, in which the normal tissues remained normal while lymphocytic infiltration reappeared in Graves' tissues. Distribution of labeled lymphocytes to the mouse organs, including the mouse thyroid, was not different between two groups. These findings further support our hypothesis that Graves' PBMCs contain memory cells that are committed to return to their autologous thyroid target and set up a gradually amplifying immune assault.