Abstract
Lymphocytes isolated from Graves' and Hashimoto thyroid tissue by enzymatic (dispase) digestion or mechanical disaggregation were markedly different in terms of their ability to synthesize thyroid autoantibodies in culture. Dispase digestion, followed by removal of thyroid follicular cells, gave a lymphocyte population with a high T:B cell ratio (6:1). However, the ability of these cell suspensions to synthesize microsomal (Mic) and thyroglobulin (Tg) antibodies spontaneously was significantly increased compared with lymphoid suspensions isolated by mechanical means. Spontaneous synthesis of thyroid autoantibodies was not markedly enhanced in cell suspensions prepared from patients' lymph node tissue by digestion compared with mechanical disaggregation. Further, Mic and Tg antibody production by thyroid lymphocytes prepared using dispase was inhibited by pokeweed mitogen (PWM) whereas in most cases suspensions prepared from the same tissues by mechanical dispersion synthesized low or undetectable levels of autoantibodies whether PWM was present or absent. Digestion of tissue debris remaining after mechanical removal of lymphocytes gave suspensions which had an increased proportion of suppressor/cytotoxic T cells compared with suspensions produced mechanically or by digestion alone; however, in terms of spontaneous autoantibody synthesis and PWM induced inhibition, these suspensions were similar to these obtained by digestion alone. It would therefore seem that enzymatic digestion of thyroid tissue resulted in the isolation of a lymphoid population which was different from that extracted by mechanical disaggregation. The digestion process appears to permit the recovery of lymphocytes closely associated with thyroid follicular cells and our studies suggest that it is this population which makes the major contribution to autoantibody synthesis.
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- Aichinger G., Fill H., Wick G. In situ immune complexes, lymphocyte subpopulations, and HLA-DR-positive epithelial cells in Hashimoto thyroiditis. Lab Invest. 1985 Feb;52(2):132–140. [PubMed] [Google Scholar]
- Atherton M. C., McLachlan S. M., Pegg C. A., Dickinson A., Baylis P., Young E. T., Proctor S. J., Rees Smith B. Thyroid autoantibody synthesis by lymphocytes from different lymphoid organs: fractionation of B cells on density gradients. Immunology. 1985 Jun;55(2):271–279. [PMC free article] [PubMed] [Google Scholar]
- BOYSE E. A., OLD L. J., CHOUROULINKOV I. CYTOTOXIC TEST FOR DEMONSTRATION OF MOUSE ANTIBODY. Methods Med Res. 1964;10:39–47. [PubMed] [Google Scholar]
- Bene M. C., Derennes V., Faure G., Thomas J. L., Duheille J., Leclere J. Graves' disease: in situ localization of lymphoid T cell subpopulations. Clin Exp Immunol. 1983 May;52(2):311–316. [PMC free article] [PubMed] [Google Scholar]
- Beverley P. C., Callard R. E. Distinctive functional characteristics of human "T" lymphocytes defined by E rosetting or a monoclonal anti-T cell antibody. Eur J Immunol. 1981 Apr;11(4):329–334. doi: 10.1002/eji.1830110412. [DOI] [PubMed] [Google Scholar]
- Brieva J. A., Stevens R. H. Inhibition of human antigen-induced lymphoblastoid B-cell function by an in vivo-induced suppressor T cell. Cell Immunol. 1983 Apr 1;77(1):109–119. doi: 10.1016/0008-8749(83)90011-4. [DOI] [PubMed] [Google Scholar]
- Hsu S. M., Jaffe E. S. Phenotypic expression of B-lymphocytes. 1. Identification with monoclonal antibodies in normal lymphoid tissues. Am J Pathol. 1984 Mar;114(3):387–395. [PMC free article] [PubMed] [Google Scholar]
- Jansson R., Karlsson A., Forsum U. Intrathyroidal HLA-DR expression and T lymphocyte phenotypes in Graves' thyrotoxicosis, Hashimoto's thyroiditis and nodular colloid goitre. Clin Exp Immunol. 1984 Nov;58(2):264–272. [PMC free article] [PubMed] [Google Scholar]
- Jansson R., Tötterman T. H., Sällström J., Dahlberg P. A. Thyroid-infiltrating T lymphocyte subsets in Hashimoto's thyroiditis. J Clin Endocrinol Metab. 1983 Jun;56(6):1164–1168. doi: 10.1210/jcem-56-6-1164. [DOI] [PubMed] [Google Scholar]
- MELLORS R. C., BRZOSKO W. J., SONKIN L. S. Immunopathology of chronic nonspecific thyroiditis (autoimmune thyroiditis). Am J Pathol. 1962 Oct;41:425–437. [PMC free article] [PubMed] [Google Scholar]
- Margolick J. B., Hsu S. M., Volkman D. J., Burman K. D., Fauci A. S. Immunohistochemical characterization of intrathyroid lymphocytes in Graves' disease. Interstitial and intraepithelial populations. Am J Med. 1984 May;76(5):815–821. doi: 10.1016/0002-9343(84)90992-6. [DOI] [PubMed] [Google Scholar]
- McLachlan S. M., Dickinson A. M., Malcolm A., Farndon J. R., Young E., Proctor S. J., Smith B. R. Thyroid autoantibody synthesis by cultures of thyroid and peripheral blood lymphocytes. I. Lymphocyte markers and response to pokeweed mitogen. Clin Exp Immunol. 1983 Apr;52(1):45–53. [PMC free article] [PubMed] [Google Scholar]
- McLachlan S. M., McGregor A., Smith B. R., Hall R. Thyroid-autoantibody synthesis by Hashimoto thyroid lymphocytes. Lancet. 1979 Jan 20;1(8108):162–163. doi: 10.1016/s0140-6736(79)90559-2. [DOI] [PubMed] [Google Scholar]
- McLachlan S. M., Pegg C. A., Atherton M. C., Middleton S., Young E. T., Clark F., Smith B. R. The effect of carbimazole on thyroid autoantibody synthesis by thyroid lymphocytes. J Clin Endocrinol Metab. 1985 Jun;60(6):1237–1242. doi: 10.1210/jcem-60-6-1237. [DOI] [PubMed] [Google Scholar]
- McLachlan S. M., Proud G., Pegg C. A., Clark F., Rees Smith B. Functional analysis of T and B cells from blood and thyroid tissue in Hashimoto's disease. Clin Exp Immunol. 1985 Mar;59(3):585–592. [PMC free article] [PubMed] [Google Scholar]
- Ollis C. A., Munro D. S., Tomlinson S. Characteristics of thyrotrophin-stimulated cyclic AMP production in cultured human thyroid cells from thyrotoxic tissue and non-toxic goitres. J Endocrinol. 1982 Nov;95(2):237–244. doi: 10.1677/joe.0.0950237. [DOI] [PubMed] [Google Scholar]
- Organization of the invading lymphoid tissue in human lymphoid thyroiditis. Scand J Immunol. 1974;3(3):295–301. doi: 10.1111/j.1365-3083.1974.tb01260.x. [DOI] [PubMed] [Google Scholar]
- Schardt C. W., McLachlan S. M., Matheson J., Smith B. R. An enzyme-linked immunoassay for thyroid microsomal antibodies. J Immunol Methods. 1982 Dec 17;55(2):155–168. doi: 10.1016/0022-1759(82)90028-x. [DOI] [PubMed] [Google Scholar]
- Stashenko P., Nadler L. M., Hardy R., Schlossman S. F. Characterization of a human B lymphocyte-specific antigen. J Immunol. 1980 Oct;125(4):1678–1685. [PubMed] [Google Scholar]
- Stevens R. H., Macy E., Morrow C., Saxon A. Characterization of a circulating subpopulation of spontaneous antitetanus toxoid antibody producing B cells following in vivo booster immunization. J Immunol. 1979 Jun;122(6):2498–2504. [PubMed] [Google Scholar]
- Warford A., McLachlan S. M., Malcolm A. J., Young E. T., Farndon J. R., Rees Smith B. Characterization of lymphoid cells in the thyroid of patients with Graves' disease. Clin Exp Immunol. 1984 Sep;57(3):626–632. [PMC free article] [PubMed] [Google Scholar]
- Weetman A. P., McGregor A. M., Lazarus J. H., Hall R. Thyroid antibodies are produced by thyroid-derived lymphocytes. Clin Exp Immunol. 1982 Apr;48(1):196–200. [PMC free article] [PubMed] [Google Scholar]
- Wilkin T. J., Casey C. The distribution of immunoglobulin-containing cells in human autoimmune thyroiditis. Acta Endocrinol (Copenh) 1984 Aug;106(4):490–498. doi: 10.1530/acta.0.1060490. [DOI] [PubMed] [Google Scholar]
- Willcox H. N., Newsom-Davis J., Calder L. R. Greatly increased autoantibody production in myasthenia gravis by thymocyte suspensions prepared with proteolytic enzymes. Clin Exp Immunol. 1983 Nov;54(2):378–386. [PMC free article] [PubMed] [Google Scholar]