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Allospecific DR gene expression on the human thyroid cell
S M Dower1, L A Piccinini, S H Roman
1Department of Medicine, Mount Sinai School of Medicine, New York.
Human thyroid epithelial cells, stimulated with recombinant gamma interferon (IF) (100 U/ml), were HLA-DR typed by means of antibody-dependent, complement-mediated cytotoxicity. The thyroid cell lysis reaction patterns were found to be similar to those obtained with autologous peripheral B cells in four of five separate experiments. Since the cytotoxic reactions with thyroid cells were sometimes incomplete with many antisera, a two-color fluorescence technique was developed to measure the specificity of the antibody-dependent, complement-mediated lysis. Using constitutively HLA-D antigen-positive Raji B lymphoblastoid cells as controls, we showed that non-polymorphic HLA-D and HLA-DR determinants could be detected on the thyroid cell surfaces by this cell lysis approach. In addition, gamma IF stimulated thyroid cells from a DR3 positive individual were lysed to a significantly greater than unstimulated autologous thyroid cells with the use of a specific monoclonal antibody to HLA-DR3, thus confirming the original HLA typing studies. These data demonstrate, for the first time, that the expression of HLA-DR antigen on the surface of human thyroid cells is allospecific and may, therefore, play an important role in the immunopathology of autoimmune thyroid disease.
Human thyroid epithelial cells, stimulated with recombinant gamma interferon (IF) (100 U/ml), were HLA-DR typed by means of antibody-dependent, complement-mediated cytotoxicity. The thyroid cell lysis reaction patterns were found to be similar to those obtained with autologous peripheral B cells in four of five separate experiments. Since the cytotoxic reactions with thyroid cells were sometimes incomplete with many antisera, a two-color fluorescence technique was developed to measure the specificity of the antibody-dependent, complement-mediated lysis. Using constitutively HLA-D antigen-positive Raji B lymphoblastoid cells as controls, we showed that non-polymorphic HLA-D and HLA-DR determinants could be detected on the thyroid cell surfaces by this cell lysis approach. In addition, gamma IF stimulated thyroid cells from a DR3 positive individual were lysed to a significantly greater than unstimulated autologous thyroid cells with the use of a specific monoclonal antibody to HLA-DR3, thus confirming the original HLA typing studies. These data demonstrate, for the first time, that the expression of HLA-DR antigen on the surface of human thyroid cells is allospecific and may, therefore, play an important role in the immunopathology of autoimmune thyroid disease.