Thyroid Infiltrating T Lymphocytes in Hashimoto’s Thyroiditis: Phenotypic and Functional Analysis at Single Cell Level

  • G. F. Del Prete
  • A. Tiri
  • S. Mariotti
  • A. Pinchera
  • S. Romagnani
  • M. Ricci

Abstract

In the last 30 years, studies of the thyroid-specific abnormal autoimmune response have mainly focused onto humoral rather than cellular mechanisms. Thus, both the initial events responsible for the breakdown in self-tolerance and the subsequent immunological mechanisms responsible for thyroid infiltration by lymphocytes and thyroid cell alterations are still poorly understood. The development of monoclonal antibodies (MoAbs) to lymphocyte membrane antigens made it possibile to analyze the phenotype of thyroid infiltrating lymphocytes by immunohistological staining techniques. Both B and T lymphocytes have been found in affected glands, the major cellular component being T cells. Some controversy, however, existed about the proportion of the CD4+and CD8+T cell subsets within autoimmune thyroid infiltrates. A reduction in intrathyroidal CD8+cells compared with peripheral blood(PB)1 or a substantial identity between PB and thyroid infiltrates with regard to the proportions of CD4+and CD8+ cells have been reported2j3.However, more recent studies agree that T cells with the CD8+ cytotoxic/suppressor phenotype are predominant in either Graves’ disease(GD) or Hashimoto’s thyroiditis (HT) infiltrates S5>6. In any case,whatever the alteration of phenotypically defined T cell population may be, it is of uncertain significance. Since it is now clear that CD4 and CD8 antigens do not represent markers of specific functions, before any conclusion is drawn on the role of a given cell population, phenotypic analysis needs to be supported by functional studies. Unfortunately, functional assays performed on heterogeneous cell populations are difficult to interpret, because they do not provide information on the proportion of cells expressing a given function.

Keywords

Interferon Thyroiditis Thyroglobulin 

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References

  1. 1.
    R. Jansson, T.H. Totterman, J. Sallstrom, and P.A. Dahlberg, Thyroid infiltrating T lymphocyte subsets in Hashimoto’s thyroiditis, J Clin Endocrinol Metab 56:1164 (1983).PubMedCrossRefGoogle Scholar
  2. 2.
    S.M. McLahlan, A.M. Dickinson, A. Malcom, J.R. Farndon, E. Young, S.J. Proctor, and B. Rees Smith, Thyroid autoantibody synthesis by cultures of thyroid, and peripheral blood lympho cytes. I. Lymphocyte markers and response to pokeweed mitogen, Clin exp Immunol 52:45 (1983).Google Scholar
  3. 3.
    J.R. Wall, R. Baur, H. Schleusener, and P. Bandy-Dafoe, Pheripheral blood and intrathyroidal mononuclear cell populations in patients witn autoimmune thyroid disorders enumerated using monoclonal antibodies, J Clin Endocrinol Metab 56:164 (1983).PubMedCrossRefGoogle Scholar
  4. 4.
    M.C. Bene, V. Derennes, G. Faure, J.L. Thomas, J. Duheille, and J. Leclere, Graves’ disease: in situ localization of lymphoid T cell subpopulations, Clin exp Immunol 52:311 (1983).PubMedGoogle Scholar
  5. 5.
    G.F. Del Prete, E. Maggi, S. Mariotti, A. Tiri, D. Vercelli, P. Parronchi, D. Macchia, A. Pinchera, M.. Ricci, S. Romagnani, Cytolytic T lymphocytes with natural killer activity in thyroid infiltrate of patients with Hashimoto’s thyroiditis: analysis at clonal level, J Clin Endocrinol Metab 62:52 (1986).PubMedCrossRefGoogle Scholar
  6. 6.
    J.B. Margolick, S.M. Hsu, D.J. Volkman, K.D. Burman, and A.S. Fauci, Immunohistochemical characterization of intrathyroid lymphocytes in Graves’ disease, Am J Med 76:815 (1984).PubMedCrossRefGoogle Scholar
  7. 7.
    G.F. Del Prete, D. Vercelli, A. Tiri, E. Maggi, S. Mariotti, A. Pinchera, M. Ricci, and S. Romagnani, In vivo activated cytotoxic T cells in the thyroid infliltrate of patients with Hashimoto’s thyroiditis, Clin exp Immunol 64:140 (1986).Google Scholar
  8. 8.
    M. Londei, G.F. Bottazzo, and M. Feldmann, Human T-cell clones from autoimmune thyroid glands: specific recognition of autologous thyroid cells, Science 228:85 (1985).PubMedCrossRefGoogle Scholar
  9. 9.
    A.P. Weetman, D.J. Volkman, K.D. Burman, J.B. Margolick, P. Petrick, B.D. Weintraub, and A.S. Fauci, The production and characterization of thyroid-derived T-cell lines in Graves’ disease and Hashimoto’s thyroiditis, Clin Immunol Immunopathol 39:139 (1986).PubMedCrossRefGoogle Scholar
  10. 10.
    A. Moretta, G. Pantaleo, L. Moretta, J.C. Cerottini, and M.C. Mingari, Direct demonstration of the clonogenic potential of every human peripheral blood T cell. Clonal analysis of HLA-DR expression and cytolytic activity, J Exp Med 157:743 (1983).PubMedCrossRefGoogle Scholar
  11. 11.
    A. Moretta, G. Pantaleo, L. Moretta, M.C. Mingari, and J.C. Cerottini, Quantitative assessment of the pool size and subset distribution of cytolytic T lymphocytes within human resting or alloactivated peripheral blood T cell populations, J Exp Med 158:571 (1983).PubMedCrossRefGoogle Scholar
  12. 12.
    G.F. Bottazzo, R. Pujol-Borrell, and T. Hanafusa, Role of aberrant HLA-DR expression and antigen presentation in induction of endocrine autoimmunity, Lancet 2:1115 (1983).PubMedCrossRefGoogle Scholar
  13. 13.
    T.F. Davies, Cocultures of human thyroid monolayer cells and autologous T cells: impact of HLA class II antigen expression, J Clin Endocrinol Metab 61:418 (1985).PubMedCrossRefGoogle Scholar
  14. 14.
    Y. Iwatani, H.C. Gerstein, M. Iitaka, V.V. Row, and R. Volpe, Thyrocyte HLA-DR expression and interferon-y production in autoimmune thyroid disease, J Clin Endocrinol Metab 63:695 (1986).PubMedCrossRefGoogle Scholar
  15. 15.
    A. Valentine, C.D. Tsoukas, G. Rhodes, J.H. Vaughan, and D.A. Carson, Phytohemagglutinin binds to the 20-KD molecule of the T3 complex, Eur J Immunol 15:851 (1985).PubMedCrossRefGoogle Scholar
  16. 16.
    G. Trinchieri, and B. Perussia, Immune interferon: a pleiotropic lymphokine with multiple effects, Immunol Today 6:131 (1985).CrossRefGoogle Scholar
  17. 17.
    S. Romagnani, M.G. Giudizi, R. Biagiotti, F. Almerigogna, M.C. Mingari, E. Maggi, C.M. Liang, and L. Moretta, B cell growth factor activity of interferon-γ. Recombinant human interferon-γ promotes proliferation of anti-μ activated human B lymphocytes J Immunol 136:3513 (1986).PubMedGoogle Scholar
  18. 18.
    M. Brunswick, and P. Lake, Obligatory role of gamma interferon in T cell replacing factor-dependent, antigen-specific murine B cell responses, J Exp Med 161:953 (1985).PubMedCrossRefGoogle Scholar
  19. 19.
    H.J. Leibson, M. Gefter, A. Zlotnik, P. Marrack, and J.W. Kappler, Role of y-interferon in antibody producing responses, Nature 309:799 (1984).PubMedCrossRefGoogle Scholar
  20. 20.
    G.F. Del Prete, S. Mariotti, A. Tiri, M. Ricci, A. Pinchera, and S. Romagnani, Characterization of thyroid infiltrating lymphocytes in Hashimoto’s thyroiditis. Detection of B and T cells specific for thyroid antigens. Acta Endocrinol (in press).Google Scholar
  21. 21.
    W.L. Farrar, H.M. Johnson, and J.J. Farrar, Regulation of the production of immune interferon and cytotoxic T lymphocytes by interleukin-2. J Immunol 126:1120 (1981).PubMedGoogle Scholar
  22. 22.
    J.R. Klein, and M.J. Bevan, Secretion of immune interferon and generation of cytotoxic T cell activity in nude mice are dependent on interleukin 2: age-associated endogenous production of interleukin 2 in nude mice. J Immunol 130:1780 (1983).PubMedGoogle Scholar
  23. 23.
    A.G. Morris, Y.L. Lin, and B.A. Askonas, Immune interferon release when a cloned cytotoxic T-cell line meets its correct influenza-infected target cell, Nature 295:151 (1982).CrossRefGoogle Scholar
  24. 24.
    Y.J. Rosenberg, A.D. Steinberg, and T.J. Santoro, The basis of autoimmunity in MRL-lpr/lpr mice: a role for self la-reactive T cells, Immunol Today 5:64 (1984).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • G. F. Del Prete
    • 1
  • A. Tiri
    • 2
  • S. Mariotti
    • 2
  • A. Pinchera
    • 1
  • S. Romagnani
    • 1
  • M. Ricci
    • 1
  1. 1.Allergology Clinical ImmunologyUniversity of FlorenceFlorenceItaly
  2. 2.EndocrinologyUniversity of Pisa Policlinico CareggiFlorenceItaly

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