Thyroid autoantigens and human T cell responses
Open Access
- 1 November 1990
- journal article
- research article
- Published by Oxford University Press (OUP) in Clinical and Experimental Immunology
- Vol. 82 (2), 275-283
- https://doi.org/10.1111/j.1365-2249.1990.tb05439.x
Abstract
We investigated the ability of T cells from patients with Hashimoto's thyroiditis and with Graves' disease as well as control donors to proliferate in response to thyroid peroxidase (TPO) and thyroglobulin using (i) lymphoid cells from different lymphoid organs; (ii) unfractionated or CD8‐depleted lymphoid suspensions or T cells+autologous low density cells (LDC); (iii) 200‐μI well cultures and 20‐μl hanging‐drop microcultures; and (iv) intact TPO and thyroglobulin, denatured thyroglobulin and 12 synthetic peptides predicted on the basis of the amino acid sequence of TPO to be T cell epitopes. In 200‐μl well cultures, proliferative responses (assessed in terms of 3H‐thymidine uptake) to intact TPO or thyroglobulin, digested thyroglobulin or synthetic TPO peptides were not significantly different in unfractionated or CD8‐depleted lymphoid suspensions from blood, thyroid or lymph nodes of TPO/thyroglobulin autoantibody‐positive patients, autoantibody‐negative patients or control donors. In contrast, blood T cells from some high titre patients with Hashimoto's thyroiditis (but not from healthy individuals) proliferated in response to intact thyroglobulin or TPO presented by autologous LDC in hanging‐drop microcultures. Heat denatured thyroglobulin (with which thyroglobulin autoantibodies do not interact) did not stimulate proliferation and this observation, together with the ability of T cells from some patients to respond to intact thyroglobulin in the absence of LDC, indicated that thyroglobulin‐specific B cells may be involved in antigen presentation. As we were unable to demonstrate proliferation by blood T cells + LDC from all thyroglobulin antibody‐positive patients with Hashimoto's thyroiditis, our studies suggest that the presence of sufficient precursor T cells, as well as the number and type of antigen‐presenting cells, are critical for T cell proliferative responses to human TPO and thyroglobulin.Keywords
This publication has 44 references indexed in Scilit:
- Mechanisms of dendritic cell functionImmunology Today, 1990
- Induction of autoimmunity with dendritic cells: Studies on thyroiditis in miceClinical Immunology and Immunopathology, 1988
- Mapping the autoimmunizing epitopes on acetylcholine receptorsImmunology Today, 1987
- Antigen processing at the molecular levelImmunology Today, 1987
- Thyroglobulin-treated blood dendritic cells induce IgG anti-thyroglobulin antibody in vitro in Hashimoto's thyroiditisClinical Immunology and Immunopathology, 1986
- How do T cells mediate autoimmune thyroiditis?Immunology Today, 1986
- Purification of the human thyroid peroxidase and its identification as the microsomal antigen involved in autoimmune thyroid diseasesFEBS Letters, 1985
- Thyroglobulin-induced T-cell in vitro proliferation in Hashimoto's thyroiditis: Identification of the responsive subset and effect of monoclonal antibodies directed to Ia antigensClinical Immunology and Immunopathology, 1984
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976
- Recherches sur la préparation et les propriétés de la thyroglobuline pure. IBiochimica et Biophysica Acta, 1948