Reduced activation of suppressor T lymphocytes by specific antigens in autoimmune thyroid disease.
In order to study the activation of suppressor T lymphocytes by thyroid-specific antigens in autoimmune thyroid disease (AITD), we have investigated the effects of the organ-specific antigens, thyroperoxidase (TPO), thyroglobulin (Tg), and thyroid microsomal antigen (TMc), as well as renal microsomes (RMc) as a control antigen, on the activation of suppressor T lymphocytes; this was accomplished by measuring major histocompatibility complex class II (HLA-DR) expression on their surfaces by flow cytometric analysis. Peripheral blood mononuclear cells (PBMC), obtained from 33 patients with Graves' disease (GD), 26 with Hashimoto's thyroiditis (HT), 5 with nontoxic nodular goiter (NTG), and 30 normal persons (N), were cultured for 7 days in the presence or absence of TPO, Tg, or RMc at final concentration of 10, 100, and 1000 ng/ml. Cultured cells were stained with fluorescent-conjugated monoclonal antibodies (anti-CD8, anti-CD11b, and anti-HLA-DR), and the activation of CD8+ and CD8+CD11b+ (pure suppressor) T cells by the antigens was analyzed on a flow cytometer. In the absence of antigen, i.e., the autologous mixed lymphocyte reaction (AMLR), CD8+ and CD8+CD11b+ T lymphocytes from patients with GD and HT showed significantly lower activation as compared to N. We measured the Stimulation Index (Sl) of activated T lymphocytes to compare antigen-specific activation between CD8+ and CD8+CD11b+ cells from normal persons and patients. With stimulation of 100 and/or 1000 ng/mL of TPO or Tg, Sl of activated CD8+ cells was significantly (p < 0.05 to 0.01) lower in GD and HT as compared with N.(ABSTRACT TRUNCATED AT 250 WORDS)
Yoshikawa
N
N
Department of Medicine, Wellesley Hospital, University of Toronto, Ontario, Canada.
Morita
T
T
Resetkova
E
E
Arreanza
G
G
Carayon
P
P
Volpé
R
R
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007453:Iodide Peroxidase / Q000276:immunology; D033862:Iron-Binding Proteins; D008213:Lymphocyte Activation / Q000502:physiology*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008861:Microsomes / Q000201:enzymology; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013954:Thyroglobulin / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology / Q000502:physiology
D000911:Antibodies, Monoclonal; D001324:Autoantigens; D016827:CD8 Antigens; D006684:HLA-DR Antigens; D033862:Iron-Binding Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D013954:Thyroglobulin; C056658:TPO protein, human; D007453:Iodide Peroxidase