Journal of Clinical Endocrinology & Metabolism, Vol 64, 818-824, Copyright © 1987 by Endocrine Society

ARTICLES

Intrathyroidal T cell clones from patients with autoimmune thyroid disease

WA MacKenzie, AE Schwartz, EW Friedman and TF Davies

We cloned activated T cells from thyroid tissue of patients with autoimmune thyroid disease. After separation on 40% Percoll gradients, T cells were cultured for 2-7 days with T cell growth factor (interleukin 2; 20 U/mL) and cloned by limiting dilution (0.3 cells/well) in the presence of irradiated autologous peripheral blood mononuclear cells (PMC; 10,000/well) as feeder cells. Fifty-seven clones were successfully expanded and tested for reactivity, cytotoxicity, helper/suppressor function, and phenotype. In the reactivity assays clones were tested for responses to autologous and allogeneic PMC, thyroid cells, human thyroglobulin (hTg), and microsomal antigen. Two distinct patterns of functional T cell clones emerged from these characterization studies. Seventy-five percent of T cell clones recovered from Graves' disease thyroid tissue (n = 21) were of helper-induced (CD4+/4B4+) phenotype, and most were effective immunoglobulin helper clones. Fifty percent of Graves' T cell clones responded to autologous PMC, and 33% had a proliferative response to autologous thyroid cells. No cytotoxic clones were derived from Graves' thyroid tissue. By contrast, intrathyroidal T cell clones from patients with autoimmune thyroiditis (n = 36) were 59% suppressor/cytotoxic (CD8+) phenotype, 17% suppressed immunoglobulin secretion, and 55% were cytotoxic to allogeneic blast cells. Fifty-five percent of clones also responded to autologous PMC, and one clone was nonspecifically autocytotoxic. In the thyroid antigen proliferation assays 11% of thyroiditis clones reacted to human thyroglobulin, but none responded to microsomal antigen. Two clones were cytotoxic to autologous but not allogeneic thyroid cells. These data demonstrate that the majority of intrathyroidal T cells in autoimmune thyroid disease are autoreactive. However, small numbers of thyroid-specific T cell clones are present within the thyroid of such patients; they are principally helper- inducer T cells in Graves' disease thyroid and cytotoxic T cells in autoimmune thyroiditis.

This article has been cited by other articles:

				S. Gullu, R. Emral, M. Bastemir, A. B Parkes, and J. H Lazarus In vivo and in vitro effects of statins on lymphocytes in patients with Hashimoto's thyroiditis Eur. J. Endocrinol., July 1, 2005; 153(1): 41 - 48. [Abstract] [Full Text] [PDF]

				G. Mazziotti, F. Sorvillo, M. Piscopo, F. Morisco, M. Cioffi, G. Stornaiuolo, G. B. Gaeta, A. M. Molinari, J. H. Lazarus, G. Amato, et al. Innate and Acquired Immune System in Patients Developing Interferon-{alpha}-Related Autoimmune Thyroiditis: A Prospective Study J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4138 - 4144. [Abstract] [Full Text] [PDF]

				B. Rapoport, G. D. Chazenbalk, J. C. Jaume, and S. M. McLachlan The Thyrotropin (TSH)-Releasing Hormone Receptor: Interaction with TSH and Autoantibodies Endocr. Rev., December 1, 1998; 19(6): 673 - 716. [Abstract] [Full Text]

				M. Okumura, Y. Hidaka, S. Kuroda, K. Takeoka, H. Tada, and N. Amino Increased Serum Concentration of Soluble CD30 in Patients with Graves' Disease and Hashimoto's Thyroiditis J. Clin. Endocrinol. Metab., June 1, 1997; 82(6): 1757 - 1760. [Abstract] [Full Text] [PDF]

				L. Guilherme, E. Cunha-Neto, V. Coelho, R. Snitcowsky, P. M. A. Pomerantzeff, R. V. Assis, F. Pedra, J. Neumann, A. Goldberg, M. E. Patarroyo, et al. Human Heart–Infiltrating T-Cell Clones From Rheumatic Heart Disease Patients Recognize Both Streptococcal and Cardiac Proteins Circulation, August 1, 1995; 92(3): 415 - 420. [Abstract] [Full Text]