Is human leukocyte antigen-DR and intercellular adhesion molecule-1 expression on human thyrocytes constitutive in papillary thyroid cancer? Comparative studies in human thyroid xenografts in severe combined immunodeficient and nude mice

J Clin Endocrinol Metab. 1998 Jan;83(1):157-64. doi: 10.1210/jcem.83.1.4489.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation
  • Carcinoma, Papillary / immunology*
  • Carcinoma, Papillary / pathology
  • Carcinoma, Papillary / surgery
  • Graves Disease / immunology
  • Graves Disease / pathology
  • Graves Disease / surgery
  • HLA-DR Antigens / analysis
  • HLA-DR Antigens / biosynthesis*
  • Humans
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / blood
  • Intercellular Adhesion Molecule-1 / analysis
  • Intercellular Adhesion Molecule-1 / biosynthesis*
  • Iodide Peroxidase / biosynthesis
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Mice
  • Mice, Nude
  • Mice, SCID
  • Neoplasm Transplantation
  • Thyroid Gland / immunology*
  • Thyroid Gland / pathology
  • Thyroid Neoplasms / immunology*
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / surgery

Substances

  • HLA-DR Antigens
  • Immunoglobulin G
  • Intercellular Adhesion Molecule-1
  • Iodide Peroxidase