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Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1993 Sep;93(3):430–436. doi: 10.1111/j.1365-2249.1993.tb08196.x

Intrathyroidal lymphocyte subsets, including unusual CD4+ CD8+ cells and CD3loTCR alpha beta lo/-CD4-CD8- cells, in autoimmune thyroid disease.

Y Iwatani 1, Y Hidaka 1, F Matsuzuka 1, K Kuma 1, N Amino 1
PMCID: PMC1554927  PMID: 8370171

Abstract

Intrathyroidal lymphocyte subsets were analysed in 13 euthyroid patients with autoimmune thyroid disease by two-colour flow cytometry and compared with subsets in peripheral blood. In both Graves' and Hashimoto's diseases, proportions of intrathyroidal CD5- B cells were higher than in peripheral blood. The numbers of such cells were correlated with serum levels of anti-thyroid microsomal antibodies. Proportions of T cells bearing alpha beta chains of T cell receptors (TCR alpha beta+ T; T alpha beta) and CD16+CD57+ natural killer (NK) cells were lower in the thyroid, but proportions of CD3hiTCR alpha beta-TCR gamma delta+ (T gamma delta) cells were not different. Proportions of CD4+Leu-8- helper T cells and CD4+CD57+ germinal centre T cells were higher and proportions of CD4+Leu-8+ suppressor-inducer T cells and CD8+CD57+ or CD8+CD11b+ suppressor T cells were lower than in the blood in both diseases. Proportions of CD5+ B cells were high in Graves' disease, and proportions of CD8+CD11b- cytotoxic T cells were high in Hashimoto's disease. Unexpectedly, CD4+CD8+ cells and CD3loTCR alpha beta lo/-CD4-CD8- cells were present in thyroid tissues of both diseases. These findings suggest that: (i) an imbalance in the numbers of regulatory T cells and of NK cells that had appeared in the thyroid resulted in the proliferation of CD5- B cells, which were related to thyroid autoantibody production; (ii) CD5+ B cells and cytotoxic T cells are important for the different pathological features in Graves' and Hashimoto's diseases, respectively; and (iii) intrathyroidal CD4+CD8+ cells and CD3loTCR alpha beta lo/-CD4-CD8- cells may be related to the pathogenesis of autoimmune thyroid disease.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abo T., Ohteki T., Seki S., Koyamada N., Yoshikai Y., Masuda T., Rikiishi H., Kumagai K. The appearance of T cells bearing self-reactive T cell receptor in the livers of mice injected with bacteria. J Exp Med. 1991 Aug 1;174(2):417–424. doi: 10.1084/jem.174.2.417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aozasa M., Amino N., Iwatani Y., Tamaki H., Matsuzuka F., Kuma K., Miyai K. Intrathyroidal HLA-DR-positive lymphocytes in Hashimoto's disease: increases in CD8 and Leu7 cells. Clin Immunol Immunopathol. 1989 Sep;52(3):516–522. doi: 10.1016/0090-1229(89)90164-5. [DOI] [PubMed] [Google Scholar]
  3. Benveniste P., Row V. V., Volpé R. Studies on the immunoregulation of thyroid autoantibody production in vitro. Clin Exp Immunol. 1985 Aug;61(2):274–282. [PMC free article] [PubMed] [Google Scholar]
  4. Beverley P. C. Is T-cell memory maintained by crossreactive stimulation? Immunol Today. 1990 Jun;11(6):203–205. doi: 10.1016/0167-5699(90)90083-l. [DOI] [PubMed] [Google Scholar]
  5. Bowen M. B., Butch A. W., Parvin C. A., Levine A., Nahm M. H. Germinal center T cells are distinct helper-inducer T cells. Hum Immunol. 1991 May;31(1):67–75. doi: 10.1016/0198-8859(91)90050-j. [DOI] [PubMed] [Google Scholar]
  6. Boyd R. L., Hugo P. Towards an integrated view of thymopoiesis. Immunol Today. 1991 Feb;12(2):71–79. doi: 10.1016/0167-5699(91)90161-L. [DOI] [PubMed] [Google Scholar]
  7. Brenner M. B., Strominger J. L., Krangel M. S. The gamma delta T cell receptor. Adv Immunol. 1988;43:133–192. [PubMed] [Google Scholar]
  8. Brieva J. A., Targan S., Stevens R. H. NK and T cell subsets regulate antibody production by human in vivo antigen-induced lymphoblastoid B cells. J Immunol. 1984 Feb;132(2):611–615. [PubMed] [Google Scholar]
  9. Canonica G. W., Caria M., Torre G., Risso A., Cosulich M. E., Bagnasco M. Autoimmune thyroid disease: purification and phenotypic analysis of intrathyroid T cells. J Endocrinol Invest. 1984 Dec;7(6):641–645. doi: 10.1007/BF03349499. [DOI] [PubMed] [Google Scholar]
  10. Clement L. T., Grossi C. E., Gartland G. L. Morphologic and phenotypic features of the subpopulation of Leu-2+ cells that suppresses B cell differentiation. J Immunol. 1984 Nov;133(5):2461–2468. [PubMed] [Google Scholar]
  11. Damle N. K., Engleman E. G. Antigen-specific suppressor T lymphocytes in man. Clin Immunol Immunopathol. 1989 Nov;53(2 Pt 2):S17–S24. doi: 10.1016/0090-1229(89)90066-4. [DOI] [PubMed] [Google Scholar]
  12. Dayan C. M., Feldmann M., Rapoport B., Londei M. Autoimmune thyroiditis and targeted anti-T cell immunotherapy in man. Autoimmunity. 1992;11(3):189–198. doi: 10.3109/08916939209035154. [DOI] [PubMed] [Google Scholar]
  13. Eguchi K., Ueki Y., Shimomura C., Otsubo T., Nakao H., Migita K., Kawakami A., Matsunaga M., Tezuka H., Ishikawa N. Increment in the Ta1+ cells in the peripheral blood and thyroid tissue of patients with Graves' disease. J Immunol. 1989 Jun 15;142(12):4233–4240. [PubMed] [Google Scholar]
  14. Gilbertson S. M., Shah P. D., Rowley D. A. NK cells suppress the generation of Lyt-2+ cytolytic T cells by suppressing or eliminating dendritic cells. J Immunol. 1986 May 15;136(10):3567–3571. [PubMed] [Google Scholar]
  15. Hassman R., Weetman A. P., Gunn C., Stringer B. M., Wynford-Thomas D., Hall R., McGregor A. M. The effects of hyperthyroidism on experimental autoimmune thyroiditis in the rat. Endocrinology. 1985 Apr;116(4):1253–1258. doi: 10.1210/endo-116-4-1253. [DOI] [PubMed] [Google Scholar]
  16. Heufelder A. E., Goellner J. R., Wenzel B. E., Bahn R. S. Immunohistochemical detection and localization of a 72-kilodalton heat shock protein in autoimmune thyroid disease. J Clin Endocrinol Metab. 1992 Apr;74(4):724–731. doi: 10.1210/jcem.74.4.1548334. [DOI] [PubMed] [Google Scholar]
  17. Ishihara T., Mori T., Waseda N., Ikekubo K., Akamizu T., Imura H. Histological, clinical and laboratory findings of acute exacerbation of Hashimoto's thyroiditis--comparison with those of subacute granulomatous thyroiditis. Endocrinol Jpn. 1987 Dec;34(6):831–841. doi: 10.1507/endocrj1954.34.831. [DOI] [PubMed] [Google Scholar]
  18. Ishikawa N., Eguchi K., Otsubo T., Ueki Y., Fukuda T., Tezuka H., Matsunaga M., Kawabe Y., Shimomura C., Izumi M. Reduction in the suppressor-inducer T cell subset and increase in the helper T cell subset in thyroid tissue from patients with Graves' disease. J Clin Endocrinol Metab. 1987 Jul;65(1):17–23. doi: 10.1210/jcem-65-1-17. [DOI] [PubMed] [Google Scholar]
  19. Iwatani Y., Amino N., Hidaka Y., Kaneda T., Ichihara K., Tamaki H., Matsuzuka F., Fukata S., Kuma K., Miyai K. Decreases in alpha beta T cell receptor negative T cells and CD8 cells, and an increase in CD4+ CD8+ cells in active Hashimoto's disease and subacute thyroiditis. Clin Exp Immunol. 1992 Mar;87(3):444–449. doi: 10.1111/j.1365-2249.1992.tb03017.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Iwatani Y., Amino N., Kaneda T., Ichihara K., Tamaki H., Tachi J., Matsuzuka F., Fukata S., Kuma K., Miyai K. Marked increase of CD5 + B cells in hyperthyroid Graves' disease. Clin Exp Immunol. 1989 Nov;78(2):196–200. [PMC free article] [PubMed] [Google Scholar]
  21. Iwatani Y., Amino N., Miyai K. Peripheral self-tolerance and autoimmunity: the protective role of expression of class II major histocompatibility antigens on non-lymphoid cells. Biomed Pharmacother. 1989;43(8):593–605. doi: 10.1016/0753-3322(89)90038-3. [DOI] [PubMed] [Google Scholar]
  22. Iwatani Y., Amino N., Mori H., Asari S., Ina K., Ennyu K., Miyai K. Effects of various isolation methods for human peripheral lymphocytes on T cell subsets determined in a fluorescence activated cell sorter (FACS), and demonstration of a sex difference of suppressor/cytotoxic T cells. J Immunol Methods. 1982 Oct 15;54(1):31–42. doi: 10.1016/0022-1759(82)90110-7. [DOI] [PubMed] [Google Scholar]
  23. Iwatani Y., Iitaka M., Row V. V., Volpé R. Effect of HLA-DR positive thyrocytes on in vitro thyroid autoantibody production. Clin Invest Med. 1988 Aug;11(4):279–285. [PubMed] [Google Scholar]
  24. Kanof M. E., Strober W., Kwan W. C., O'Connell N. A., James S. P. CD4+ Leu-8+ T cell supernatant activity that inhibits Ig production. J Immunol. 1991 Jul 1;147(1):155–161. [PubMed] [Google Scholar]
  25. Kansas G. S., Wood G. S., Fishwild D. M., Engleman E. G. Functional characterization of human T lymphocyte subsets distinguished by monoclonal anti-leu-8. J Immunol. 1985 May;134(5):2995–3002. [PubMed] [Google Scholar]
  26. Koga T., Wand-Württenberger A., DeBruyn J., Munk M. E., Schoel B., Kaufmann S. H. T cells against a bacterial heat shock protein recognize stressed macrophages. Science. 1989 Sep 8;245(4922):1112–1115. doi: 10.1126/science.2788923. [DOI] [PubMed] [Google Scholar]
  27. Koide J., Engleman E. G. Differences in surface phenotype and mechanism of action between alloantigen-specific CD8+ cytotoxic and suppressor T cell clones. J Immunol. 1990 Jan 1;144(1):32–40. [PubMed] [Google Scholar]
  28. Lahat N., Sheinfeld M., Sobel E., Baron E., Kraiem Z. Class II HLA-DR antigens on non-autoimmune human thyroid cells stimulate autologous T cells with high suppressor activity. Autoimmunity. 1990;8(2):125–133. doi: 10.3109/08916939008995730. [DOI] [PubMed] [Google Scholar]
  29. Lebow L. T., Bonavida B. Purification and characterization of cytolytic and noncytolytic human natural killer cell subsets. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6063–6067. doi: 10.1073/pnas.87.16.6063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lider O., Miller A., Miron S., Hershkoviz R., Weiner H. L., Zhang X. M., Heber-Katz E. Nonencephalitogenic CD4-CD8- V alpha 2V beta 8.2+ anti-myelin basic protein rat T lymphocytes inhibit disease induction. J Immunol. 1991 Aug 15;147(4):1208–1213. [PubMed] [Google Scholar]
  31. MacKenzie W. A., Schwartz A. E., Friedman E. W., Davies T. F. Intrathyroidal T cell clones from patients with autoimmune thyroid disease. J Clin Endocrinol Metab. 1987 Apr;64(4):818–824. doi: 10.1210/jcem-64-4-818. [DOI] [PubMed] [Google Scholar]
  32. Mackenzie W. A., Davies T. F. An intrathyroidal T-cell clone specifically cytotoxic for human thyroid cells. Immunology. 1987 May;61(1):101–103. [PMC free article] [PubMed] [Google Scholar]
  33. Martin A., Goldsmith N. K., Friedman E. W., Schwartz A. E., Davies T. F., Roman S. H. Intrathyroidal accumulation of T cell phenotypes in autoimmune thyroid disease. Autoimmunity. 1990;6(4):269–281. doi: 10.3109/08916939008998419. [DOI] [PubMed] [Google Scholar]
  34. Masuda T., Ohteki T., Abo T., Seki S., Nose S., Nagura H., Kumagai K. Expansion of the population of double negative CD4-8- T alpha beta-cells in the liver is a common feature of autoimmune mice. J Immunol. 1991 Nov 1;147(9):2907–2912. [PubMed] [Google Scholar]
  35. McLachlan S. M., Pegg C. A., Atherton M. C., Middleton S. L., Clark F., Rees Smith B. TSH receptor antibody synthesis by thyroid lymphocytes. Clin Endocrinol (Oxf) 1986 Feb;24(2):223–230. doi: 10.1111/j.1365-2265.1986.tb00766.x. [DOI] [PubMed] [Google Scholar]
  36. Mosley R. L., Styre D., Klein J. R. CD4+CD8+ murine intestinal intraepithelial lymphocytes. Int Immunol. 1990;2(4):361–365. doi: 10.1093/intimm/2.4.361. [DOI] [PubMed] [Google Scholar]
  37. Palathumpat V., Dejbakhsh-Jones S., Holm B., Wang H., Liang O., Strober S. Studies of CD4- CD8- alpha beta bone marrow T cells with suppressor activity. J Immunol. 1992 Jan 15;148(2):373–380. [PubMed] [Google Scholar]
  38. Paliard X., Malefijt R. W., de Vries J. E., Spits H. Interleukin-4 mediates CD8 induction on human CD4+ T-cell clones. Nature. 1988 Oct 13;335(6191):642–644. doi: 10.1038/335642a0. [DOI] [PubMed] [Google Scholar]
  39. Pilarski L. M., Yacyshyn B. R., Jensen G. S., Pruski E., Pabst H. F. Beta 1 integrin (CD29) expression on human postnatal T cell subsets defined by selective CD45 isoform expression. J Immunol. 1991 Aug 1;147(3):830–837. [PubMed] [Google Scholar]
  40. Prud'Homme G. J., Bocarro D. C., Luke E. C. Clonal deletion and autoreactivity in extrathymic CD4-CD8-(double negative) T cell receptor-alpha/beta T cells. J Immunol. 1991 Nov 15;147(10):3314–3318. [PubMed] [Google Scholar]
  41. Seki S., Abo T., Ohteki T., Sugiura K., Kumagai K. Unusual alpha beta-T cells expanded in autoimmune lpr mice are probably a counterpart of normal T cells in the liver. J Immunol. 1991 Aug 15;147(4):1214–1221. [PubMed] [Google Scholar]
  42. Shivakumar S., Tsokos G. C., Datta S. K. T cell receptor alpha/beta expressing double-negative (CD4-/CD8-) and CD4+ T helper cells in humans augment the production of pathogenic anti-DNA autoantibodies associated with lupus nephritis. J Immunol. 1989 Jul 1;143(1):103–112. [PubMed] [Google Scholar]
  43. Swat W., Ignatowicz L., von Boehmer H., Kisielow P. Clonal deletion of immature CD4+8+ thymocytes in suspension culture by extrathymic antigen-presenting cells. Nature. 1991 May 9;351(6322):150–153. doi: 10.1038/351150a0. [DOI] [PubMed] [Google Scholar]
  44. Teng W. P., Cohen S. B., Posnett D. N., Weetman A. P. T cell receptor phenotypes in autoimmune thyroid disease. J Endocrinol Invest. 1990 Apr;13(4):339–342. doi: 10.1007/BF03349575. [DOI] [PubMed] [Google Scholar]
  45. Tezuka H., Eguchi K., Fukuda T., Otsubo T., Kawabe Y., Ueki Y., Matsunaga M., Shimomura C., Nakao H., Ishikawa N. Natural killer and natural killer-like cell activity of peripheral blood and intrathyroidal mononuclear cells from patients with Graves' disease. J Clin Endocrinol Metab. 1988 Apr;66(4):702–707. doi: 10.1210/jcem-66-4-702. [DOI] [PubMed] [Google Scholar]
  46. Tötterman T. H. Distribution of T-, B-, and thyroglobulin-binding lymphocytes infiltrating the gland in Graves' disease, Hashimoto's thyroiditis, and de Quervain's thyroiditis. Clin Immunol Immunopathol. 1978 Jul;10(3):270–277. doi: 10.1016/0090-1229(78)90181-2. [DOI] [PubMed] [Google Scholar]
  47. Tötterman T. H., Karlsson F. A., Bengtsson M., Mendel-Hartvig I. Induction of circulating activated suppressor-like T cells by methimazole therapy for Graves' disease. N Engl J Med. 1987 Jan 1;316(1):15–22. doi: 10.1056/NEJM198701013160104. [DOI] [PubMed] [Google Scholar]
  48. Ueki Y., Eguchi K., Otsubo T., Kawabe Y., Shimomura C., Matsunaga M., Tezuka H., Nakao H., Kawakami A., Izumi M. Phenotypic analyses and concanavalin-A-induced suppressor cell dysfunction of intrathyroidal lymphocytes from patients with Graves' disease. J Clin Endocrinol Metab. 1988 Nov;67(5):1018–1024. doi: 10.1210/jcem-67-5-1018. [DOI] [PubMed] [Google Scholar]
  49. Walfish P. G., Tseng K. H. Intrathyroidal activated (Ia+) T-lymphocyte CD+ subsets and B cells in Graves' hyperthyroidism respond rapidly to propylthiouracil therapy: demonstration using fine needle aspirates and two-colour laser flow cytometry. Autoimmunity. 1992;13(1):35–41. doi: 10.3109/08916939209014633. [DOI] [PubMed] [Google Scholar]
  50. Webb S., Morris C., Sprent J. Extrathymic tolerance of mature T cells: clonal elimination as a consequence of immunity. Cell. 1990 Dec 21;63(6):1249–1256. doi: 10.1016/0092-8674(90)90420-j. [DOI] [PubMed] [Google Scholar]
  51. 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]
  52. Yoshida H., Amino N., Yagawa K., Uemura K., Satoh M., Miyai K., Kumahara Y. Association of serum antithyroid antibodies with lymphocytic infiltration of the thyroid gland: studies of seventy autopsied cases. J Clin Endocrinol Metab. 1978 Jun;46(6):859–862. doi: 10.1210/jcem-46-6-859. [DOI] [PubMed] [Google Scholar]

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