Successful production of intrathyroidal human T cell hybridomas: evidence for intact helper T cell function in Graves' disease.
We have developed a series of human intrathyroidal T-T cell hybridomas and evaluated their phenotypic characteristics and lymphokine secretions in order to further understand the role of the T cell in Graves' disease. Mitogen-stimulated T cell blasts were generated from intrathyroidal lymphocyte preparations and fused with a hypoxanthine-, aminopterin-, and thymidine-sensitive variant of the Molt 4 human leukemia T cell line. The resulting intrathyroidal T-T cell hybridomas and T-T cell hybridomas obtained from normal peripheral blood mitogen-stimulated T cell blasts were expanded and tested for their biological function. None of the generated T cell hybridomas exhibited antigen-specific IL-2 secretion when stimulated with autologous thyrocytes, although 60% of the hybridomas expressed CD3 antigen and the T cell receptor alpha/beta heterodimer. However, 9 intrathyroidal and 11 peripheral blood T cell hybridomas secreted a factor(s) that significantly enhanced immunoglobulin G secretion in vitro (P less than 0.005, by Student-Newman-Keuls test; mean +/- SEM, 338 +/- 60% increase). In summary, we have successfully used a technique that allows the construction of T-T cell hybridomas derived from intrathyroidal T cell cultures. The data demonstrated that a predominance of helper factor-secreting T cells were available for fusion within the Graves' thyroid gland. Such observations are further evidence for intact T cell help within the thyroid gland of patients with Graves' disease.
Martin
A
A
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029.
Schwartz
A E
AE
Friedman
E W
EW
Davies
T F
TF
D000236:Adenoma / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006111:Graves Disease / Q000276:immunology*; D006801:Humans; D006825:Hybridomas / Q000276:immunology*; D007074:Immunoglobulin G / Q000032:analysis; D007376:Interleukin-2 / Q000096:biosynthesis; D012016:Reference Values; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013961:Thyroid Gland / Q000276:immunology*; D013964:Thyroid Neoplasms / Q000276:immunology
D007074:Immunoglobulin G; D007376:Interleukin-2