Different immunophenotype and autoantibody production by peripheral blood and thyroid-derived lymphocytes in patients with Graves' disease.
Direct multi-colour flow cytometric analysis was employed in patients with Graves' disease (n = 10) to determine the immunophenotype in peripheral blood lymphocytes (PBL) at the time of diagnosis without treatment (PBLw) and prior to operation (PBLp) and in thyroid-derived lymphocytes (TL). Additionally, the secretion of anti-thyroperoxidase antibodies (anti-TPO) was measured during culture of isolated peripheral or thyroid-derived B cells. Among TL from patients with high serum levels of anti-TPO (6/10) a significantly (p < 0.01) higher percentage of B cells were detected compared to PBLp (TL: 21.7 +/- 7.2%; PBLp: 13.2 +/- 4.5%). Enriched thyroid-derived B cells only from these patients also showed high spontaneous anti-TPO secretion during culture. The difference between peripheral and thyroid-derived natural killer (NK) cells was highly significant (p < 0.001; TL: 5.6 +/- 6.3%; PBLp: 13.6 +/- 5.5%). Two patients were found with a higher number of NK cells within TL. These patients were among those who had a low number of B cells infiltrating the thyroid gland. Regarding the expression of several other differentiation antigens, i.e. CD4 and CD8, gamma/delta TCR bearing T cells and CD45R0 on CD4+ T cells as a marker for memory cells, on TL no differences could be detected between patients with or without anti-TPO. In TL 31.5 +/- 7.7% of CD3- cells expressed the HLA-DR antigen (vs. 6.1 +/- 2.4% in PBLp; p < 0.001). Half of these cells simultaneously expressed the activation antigen CD69. Surprisingly, the number of CD3+ TL bearing the IL-2 receptor (CD25) and transferrin receptor (CD71) was not increased. Taken together, the proportional distribution of B and NK cells within the thyroid correlates with the anti-TPO secretion in vivo and in vitro, suggesting different immune response regulation processes of TL.
Aust
G
G
Department of Internal Medicine III, University of Leipzig, Germany.
Lehmann
I
I
Heberling
H J
HJ
D000328:Adult; D000917:Antibody Formation; D015703:Antigens, CD / Q000032:analysis; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology*; D017252:CD3 Complex / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006111:Graves Disease / Q000097:blood / Q000276:immunology* / Q000628:therapy; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D007453:Iodide Peroxidase / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*; D013961:Thyroid Gland / Q000276:immunology*
D015703:Antigens, CD; D001323:Autoantibodies; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D006684:HLA-DR Antigens; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007453:Iodide Peroxidase; D017493:Leukocyte Common Antigens