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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 Mice¹

Endocrinology Research Laboratory, Departments of Medicine (K.K., E.R., T.E., R. V.) and Pathology (V.F), The Wellesley Hospital, University of Toronto, Toronto, Ontario, M4Y1J3, Canada.

Address all correspondence and requests for reprints to: Professor Robert Volpé, Endocrinology Research Laboratory, The Wellesley Hospital, University of Toronto, 160 Wellesley Street East, 112D Jones Building, Toronto, Ontario, M4Y1J3, Canada.

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.

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