Is Human Leukocyte Antigen-DR and Intercellular Adhesion Molecule-1 Expression on Human Thyrocytes Constitutive in Papillary Thyroid Cancer? Comparative Studies of Human Thyroid Xenografts in Severe Combined Immunodeficient and Nude Mice

Abstract

We have studied human leukocyte antigen (HLA)-DR and intercellular adhesion molecule (ICAM)-1 expression on thyroid epithelial cells (TEC) from papillary thyroid carcinoma (PTC) tissues xenografted into two different mouse strains [the severe combined immunodeficient (SCID) mouse, which accepts human tissue with lymphocytes; and the nude mouse, which accepts the tissue but destroys all passenger lymphocytes]. Human PTC [PTC/TIL (PTC with tumor infiltrating lymphocytes) and PTC/PTC (PTC without tumor infiltrating lymphocytes)], Graves' disease (GD), and normal thyroid (N) tissues were xenografted sc into 22 SCID and 21 nude mice. Blood samples were taken every 2 weeks for measurement of human IgG and thyroid antibodies. Seven weeks after xenografting, xenografted thyroid tissues were analyzed for thyrocyte HLA-DR and ICAM-1 expression. SCID mice xenografted with PTC/TIL (PTC/TIL-SCID) manifested IgG production for 6 weeks, but nude mice showed diminished and disappearing IgG production from these xenografts. Thyroperoxidase (TPO)-antibody (Ab)(TPO-Ab) was not detectable in PTC/TIL-SCID despite the presence of TPO-Ab in some donors. Thyroglobulin-Ab (Tg-Ab) was detectable in all mice of PTC/TIL-SCID. Thyrocyte HLA-DR expression from PTC-SCID was markedly increased, compared with that from nude mice xenografts or from N xenografts in SCID mice. In addition, thyrocyte HLA-DR expression from PTC-nude was markedly increased, compared with the expression seen in GD-nude and N-nude xenografts. ICAM-1 expression on TEC from PTC xenografts in the SCID mouse was markedly increased, compared with N xenografts. ICAM-1 expression on TEC from PTC did not show any difference between SCID and nude mice. ICAM-1 expression on TEC from PTC xenografts in the nude mice was markedly increased, compared with those from GD and N xenografts. In conclusion, TIL in PTC produce Tg-Ab but do not produce TPO-Ab. HLA-DR expression on TEC from PTC is strongly constitutive, but it is also affected by TIL. TIL might have some role in control of PTC through partial expression of HLA-DR on TEC. ICAM-1 expression on TEC from PTC seems to be entirely constitutive, and it is not affected by the presence of local lymphocytes, in contrast to autoimmune thyroid disease.