Microsomal antigen-reactive lymphocyte lines and clones derived from thyroid tissue of patients with Graves' disease.
Thyroid mononuclear cells (TMC) were maintained in long term cocultures with thyroid fibroblasts and thyroid epithelial cells from patients with Graves' disease, using medium supplemented with thyroid microsomal antigen (McAg) and IL-2. The TMC consisted predominantly of T4+ (CD4+, helper) and, to a lesser extent, T8+ (CD8+, cytotoxic/suppressor) lymphocytes, with a small number of macrophages and natural killer cells. The average T4+ to T8+ ratio was 3.2. From these cultures we obtained thyroid T cell lines and clones reactive to thyroid antigens. T Cell lines were tested in a microproliferation assay using thyroglobulin (Tg), McAg, tetanus toxoid, and IL-2. Of 14 lines from 6 patients, 2 proliferated in response to McAg when TMC plus thyroid fibroblasts were used as antigen-presenting cells. Clones of thyroid lymphocytes were obtained by culturing cells at limiting dilution with IL-2, McAg, and different types of autologous accessory cells. Peripheral blood mononuclear cells plus skin fibroblasts provided the best source of accessory cells, allowing near 100% cloning efficiency. Of 26 clones tested, 6 recognized McAg, 2 were Tg reactive, and 3 were autoreactive. All phenotyped clones were of the T4+ phenotype. Our method results in production of thyroid T cell lines and clones. The fibroblasts probably provided growth factors and/or collaborated with peripheral blood mononuclear cells as antigen-presenting cells. These lines and clones from patients with Graves' disease were predominantly helper T cells, in contrast to the previously demonstrated cytotoxic/suppressor cell predominance in cells from patients with Hashimoto's thyroiditis. This difference in cell function may help explain the differing clinical courses of these two closely related autoimmune thyroid diseases. The availability of long term microsomal antigen-specific T cell clones should allow careful analysis of the role these cells play in thyroid autoimmunity.
Fisfalen
M E
ME
Department of Medicine, University of Chicago, Illinois 60637.
DeGroot
L J
LJ
Quintans
J
J
Franklin
W A
WA
Soltani
K
K
D000941:Antigens / Q000276:immunology*; D002478:Cells, Cultured; D002999:Clone Cells / Q000276:immunology; D004848:Epithelium / Q000473:pathology; D005347:Fibroblasts / Q000276:immunology; D006111:Graves Disease / Q000276:immunology* / Q000473:pathology; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D008861:Microsomes / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D013961:Thyroid Gland / Q000276:immunology / Q000473:pathology*
D000941:Antigens; D006684:HLA-DR Antigens