Successful Production of Intrathyroidal Human T Cell Hybridomas: Evidence for Intact Helper T Cell Function in Graves’ Disease*

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Abstract
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 < 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.