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At least 19 recordsLinked to original sources
PubMed1994

Thyroid antibodies in association with thyroid malignancy. I. Simultaneous occurrence of thyroiditis and thyroid malignancy.

Occurrence of thyroid antibodies and thyroiditis in association with thyroid malignancy, suspected malignancy or other thyroid diseases was studied in 177 patients. Retrospective clinical analysis revealed that 137 patients had thyroid carcinoma (108 papillary carcinomas, 10 occult papillary carcinomas, 14 follicular carcinomas, and 5 other carcinomas) and 40 had other thyroid diseases. Thyroid microsomal (AMC) and thyroglobulin antibodies (ATG) were measured by the particle agglutination method. Clinically significant thyroid antibody titers and histological or clinical features of thyroiditis were seen in nine patients with thyroid carcinoma, being equally prevalent in follicular and papillary carcinomas. Taking into account the prevalence of positive AMC antibodies and thyroid carcinoma in Finland, the highest predicted prevalence of simultaneously occurring thyroid carcinoma and thyroiditis in the under 40 age group should be 0.002% and in the over 40 age group 0.006%. In the present material the observed occurrences in corresponding age groups were unexpectedly high (4.7% and 5.2%). The results may partly be due to patient selection, but they also suggest that there might be a link between thyroiditis and thyroid carcinoma.

Adolescent↗
PubMed1986

The differences of susceptibility of the target thyroid gland to autoimmune thyroiditis and of antigenicity of thyroid gland for induction of experimental autoimmune thyroiditis.

By using a recently developed method for producing thyroiditis in mice consisting of implantation of a fresh thyroid gland into the peritoneal cavity or under the capsule of the kidney with subsequent injection of lipopolysaccharide, differences were shown in susceptibility of the target thyroid gland to autoimmune destruction and in antigenicity of the thyroid gland for induction of experimental autoimmune thyroiditis. Using recombinant congenic mice, the H-2 haplotypes of the target thyroid gland were found to be as important as those of the immune system in development of autoimmune thyroiditis. On the other hand, the H-2 haplotypes of the thyroid gland are unimportant for induction of autoimmune thyroiditis.

Animals↗
PubMed1995

c-Kit proto-oncogene is more likely to lose expression in differentiated thyroid carcinoma than three thyroid-specific genes: thyroid peroxidase, thyroglobulin, and thyroid stimulating hormone receptor.

Although c-kit proto-oncogene product is known to be weakly expressed on normal thyrocytes, its function is unclear. In order to investigate the significance of thyroid c-kit, c-kit gene expression in 37 various thyroid tissues was analyzed by comparing c-kit gene expression with the mRNA expression of three thyroid-specific genes: thyroid peroxidase, thyroglobulin, and thyroid stimulating hormone receptor, c-kit mRNA was hardly detected by the usual northern blot method in 2 of 7 follicular carcinomas, 11 of 12 papillary carcinomas, and a medullary carcinoma. On the other hand, a high level of c-kit mRNA expression was found in all 17 benign thyroid tissues (4 normal thyroid tissues, 4 Graves' disease, 2 adenomatous goiters, and 7 follicular adenomas). This study found that c-kit proto-oncogene is more likely to lose expression in differentiated thyroid carcinoma than any thyroid-specific gene. Decreased c-kit gene expression may serve as an indicator for the de-differentiation of thyrocytes.

Blotting, Northern↗
PubMed1994

Anti-thyroid peroxidase (anti-TPO) antibodies in thyroid diseases, non-thyroidal illness and controls. Clinical validity of a new commercial method for detection of anti-TPO (thyroid microsomal) autoantibodies.

The identification of the thyroid peroxidase (TPO) as the main antigen of the thyroid microsomal fraction has enabled the development of a sensitive and specific assay for detection of the corresponding autoantibodies. We evaluated the diagnostic validity of the anti-TPO assay in 303 patients with different types of thyroid disease and in controls. Clearly elevated anti-TPO values (anti-TPO > 500 units/ml) were found in 59% of patients with thyroiditis but in none of the controls or the patients with non-thyroidal illness. The mean anti-TPO levels in these two control groups were 26 +/- 31 units/ml (mean +/- S.D.) and 39 +/- 34 units/ml, respectively. The highest frequency of positive results (88%) was obtained in patients with auto-immune hypothyroidism (clinical diagnosis: Hashimoto's thyroiditis) followed by patients with Graves' disease (53%). With a cut-off point of 200 units/ml, a sensitivity of 96% was obtained for Hashimoto's thyroiditis and of 59% for Graves' disease with a specificity of 100% (50 cases). The new method (anti-TPO, Dynotest) was compared with three conventional methods (35 samples). The results for all measurements were in general agreement. In two cases the results were clearly discordant: one sample contained high anti-thyroglobulin antibody concentrations, the other was obtained from a patient with non-thyroidal illness. In both instances the 'classical' assays yielded false-positive results. Treatment of autoimmune hyperthyroidism resulted in a median decrease in anti-TPO levels of over 50% after reaching the euthyroid state (P < 0.05), whereas in persistent hyperthyroidism no consistent changes were observed. In autoimmune hypothyroidism a marked variability in anti-TPO levels was noted. Some patients showed a clear decrease in anti-TPO levels during T4 substitution whereas in others no consistent changes were observed.

Autoantibodies↗
PubMed1987

The thyroid microenvironment in autoimmune thyroid disease: effects of TSH and lymphokines on thyroid lymphocytes and thyroid cells.

Thyroid lymphocytes synthesize thyroid autoantibodies in close proximity to thyroid cells and consequently soluble mediators such as TSH and interleukins (IL) 1 and 2 may have unforeseen effects on lymphocytes and thyrocytes, respectively. Investigations of thyroid autoantibody synthesis by thyroid lymphocytes in vitro showed that TSH did not affect microsomal (Mic) antibody production, but thyroglobulin (Tg) antibody synthesis was decreased, probably as a result of complexing between Tg antibody and Tg secreted by small numbers of thyrocytes in the cell suspension. IL-1 and IL-2 partially mimicked the inhibitory effects on spontaneous autoantibody synthesis induced by Pokeweed mitogen (PWM) in cultures of thyroid lymphocytes. This inhibition may require a number of soluble mediators released by T cells in response to the mitogen; however, depletion studies indicated that the cell type responsible for PWM inhibition is unlikely to be a suppressor T cell and may be an NK cell. IL-1 and IL-2 had little effect on the viability of thyrocyte monolayers in an 18 h assay, but antibody dependent cells cytotoxicity (ADCC) using blood lymphocytes and thyroid autoantibody positive sera was demonstrated; further, the cytotoxicity appeared to be due to Mic antibodies. It is possible that IL-1 and/or IL-2 (as well as other cytokines) may affect thyroid cells after longer periods of exposure, either by altering them functionally or by direct damage. However, assuming that NK cells are present in sufficient numbers in the gland, ADCC could play a major role in the development of hypothyroidism in Hashimoto's disease.

Cells, Cultured↗
PubMed1977

Comparison of thyroid antigens by the experimental production of precipitating antibodies to human thyroid fractions and the identification of an antibody which competes with long-acting thyroid stimulator (LATS) for thyroid binding.

Antibodies were raised to various sub-cellular fractions of human thyroids, (of Graves' disease, Hashimoto's thyroiditis, and non-toxic goitre). With one exception it was found that antibodies to the Graves' thyroid fractions crooss-reacted with both the non-toxic goitre and Hashimoto's thyroiditis fractions. This exception was in the antiserum to the Graves' 105 000 x g pellet (Gr4) which contained an anr the Hashimoto's (/) thyroid preparations. The antibody-antigen between A-1 and Gr4 could be blocked by the addition of LATS (or TSH) to the antigen, thus suggesting that A- 1 might be a LATS-like immunoglobulin. These results suggest that the TSH receptor can be produced in vivo. Production of such an antibody to the TSH receptor would permit the development for the first time fo a good animal model of Graves' disease.

Antibody Specificity↗
PubMed1975

A radio-ligand receptor assay for the long-acting thyroid stimulator. Inhibition by the long-acting thyroid stimulator of the binding of radioiodinated thyroid-stimulating hormone to human thyroid membranes.

Highly purified bovine TSH (thyroid-stimulating hormone) was labelled with 125I by using very low concentrations of chloramine-T. Human thyroid membranes prepared by discontinuous sucrose-density-gradient centrifugation were homogeneous on examination by electron microscopy. Incubation of radioiodinated TSH with the membranes showed that radioactivity could be bound to the membranes. Under the experimental conditions described here, binding was dependent on time and temperature and was a saturable phenomenon. Preincubation of the membranes with unlabelled hormone inhibited the subsequent binding of 125I-labelled TSH. Similarly, inhibition by the long-acting thyroid stimulator also showed a saturation behaviour. A rapid and sensitive method for the detection of the long-acting thyroid stimulator is described.

Cell Membrane↗
PubMed1980

Incidence of malignant thyroid tumors in humans after exposure to diagnostic doses of iodine-131. II. Estimation of thyroid gland size, thyroid radiation dose, and predicted versus observed number of malignant thyroid tumors.

The size of the thyroid glands was analyzed for 10% of the patients in a selected group that had been exposed to diagnostic doses of 131I. The mean thyroid gland weight +/- SD was 50 +/- 33 g for patients 20 or more years of age and 10 +/- 5 g for patients less than 20 years of age. With the present follow-up, diagnostic doses of 131I appeared not to be associated with an increased risk for later development of malignant thyroid tumors. Possible reasons for the difference between the observed number of such tumors and the number expected (47-124) on the basis of risk estimates of the United Nations Scientific Committee on the Effects of Atomic Radiation are discussed.

Dose-Response Relationship, Radiation↗
PubMed1991

Why no simple relationship between thyroid peroxidase activity-inhibiting immunoglobulins and thyroid function in autoimmune thyroid disease?

We have reported that some anti-thyroid peroxidase antibodies inhibit the activity of thyroid peroxidase in vitro. These thyroid peroxidase activity-inhibiting immunoglobulins seem to inhibit thyroid function in some patients, but the relationship between thyroid peroxidase activity-inhibiting immunoglobulins and thyroid function is not simple. We designed this study to explore this lack of a simple relationship. We stained immunoglobulin G deposits by immunofluorescence staining or the peroxidase-antiperoxidase method, and stained endogenous thyroid peroxidase activity by enzyme histochemistry in thyroid sections. When cryostat thyroid sections were incubated with thyroid peroxidase activity-inhibiting immunoglobulins, immunoglobulin G deposits were seen as lines of stain on the apical border and as intracellular staining, and endogenous thyroid peroxidase activity was inhibited. In paraffin-embedded thyroid sections from 5 Hashimoto's patients and 6 Graves' patients, immunoglobulin G deposits were not found on the apical border of the follicular epithelium. In frozen thyroid sections from 22 Graves' patients, no clear deposits of immunoglobulin G on this apical border were seen. In organ-cultured thyroid slices incubated with thyroid peroxidase activity-inhibiting immunoglobulins, endogenous thyroid peroxidase activity was not inhibited. In conclusion, thyroid peroxidase activity-inhibiting immunoglobulins may reach its antigen only with difficulty. This is one of the reasons why no simple relationship is observed between thyroid peroxidase activity-inhibiting immunoglobulins and thyroid function.

Antigens↗
PubMed1990

Physiological de novo thyroid hormone formation in primary culture of porcine thyroid follicles: adenosine 3',5'-monophosphate alone is sufficient for thyroid hormone formation.

We describe a method of culturing intact porcine thyroid follicles for physiological de novo thyroid hormone formation; the roles of cAMP and protein kinase-C in thyroid hormone formation were also studied. Thyroid follicles were obtained by digesting minced porcine thyroid tissue with 0.04% collagenase and cultured in Coon's Modified Ham's F-12 medium supplemented with 0.5% calf serum, 0.5 mU/ml TSH, other standard hormones, and 3 antibiotics (6H medium). On the fourth day of culture, 6000-8000 follicles/well were plated in 12-well culture dishes. On the sixth day, thyroid hormone formation was carried out by incubating thyroid follicles with 0.5 microM KI in the presence of 6H medium for 2 days in a 5% CO2-95% air incubator at 37 C. To examine the effects of cAMP and protein kinase-C on de novo thyroid hormone formation, follicles were incubated with KI in the presence of 1-2.5 mM (Bu)2cAMP, 10 microM forskolin, 2 microM prostaglandin E2 (PGE2), or 0.5-1 microM 12-O-tetradecanoylphorbol-13-acetate in TSH-free medium for 2 days. The amount of newly formed thyroid hormone was measured by RIA of T3 content in the Pronase digest of thyroid follicular cells. Thyroid follicles cultured in 6H medium had normal polarity of the membrane, determined by electron microscope, and thyroid cAMP was responsive to the alteration of TSH. In this culture system cAMP alone was sufficient to form thyroid hormone. 12-O-Tetradecanoylphorbol-13-acetate, a protein kinase-C stimulator, disrupted thyroid follicles and inhibited cAMP-mediated thyroid hormone formation. The integrity of follicular structure was also required for thyroid hormone formation in this culture system. This study introduces perhaps the most physiological culture system for de novo thyroid hormone formation. Our data provide direct evidence that thyroid hormone formation is linked to cAMP and that the protein kinase-C system acts as an inhibitor of thyroid hormone formation.

Animals↗
PubMed2001

Thyroid ultrasonography as a tool for detecting thyroid autoimmune diseases and predicting thyroid dsfunction in apparently healthy subjects.

UNLABELLED: In order to establish its usefulness for the diagnosis and follow-up of thyroid autoimmune diseases, thyroid ultrasonography together with free T4 (FT4), free T3 (FT3), TSH, antibodies (Tg Ab) and thyroperoxidase antibodies (TPO Ab) were performed and re-evaluated during a 3-yr follow-up in 482 apparently healthy subjects, living in a borderline iodine-sufficient urban area. Thyroid dysfunction was found in 7 out of 12 (58.3%) subjects with circulating thyroid autoantibodies, who also had thyroid hypoechogenicity (2 had overt and 3 subclinical hypothyroidism at booking; 2 developed subclinical hypothyroidism during the follow-up), and in none of the 12 subjects with normal thyroid echostructure (chi2=7.26, p=0.007). Thyroid dysfunction was found in 4 out of 29 (13.7%) subjects with negative Tg and/or TPO Ab who also had thyroid hypoechogenicity (1 had Graves' disease at booking, 1 developed Graves' disease and 2 subclinical hypothyroidism during the follow-up), and in none of the 429 with normal thyroid echostructure (chi2=82.03, p<0.0001). Although positive TPO and/or Tg Ab were more frequent (24/482, 5%) in subjects with thyroid dysfunction (7/11) than in those who remained euthyroid during the study (17/471, chi2=69.66, p<0.0001), thyroid hypoechogenicity had a higher sensitivity than the positivity of thyroid autoantibody tests (100 vs 63.3%) for diagnosing or predicting thyroid dysfunction. IN CONCLUSION: 1) thyroid ultrasonography is a useful tool to detect thyroid autoimmune disease in apparently healthy subjects; 2) present and future thyroid dysfunction is more readily predicted by a hypoechogenic pattern at thyroid ultrasound than by the occurrence of serum thyroid autoantibodies.

Adolescent↗
PubMedDate not supplied

Coexisting Hashimoto's thyroiditis with differentiated thyroid cancer and benign thyroid diseases: indications for thyroidectomy.

Hashimoto's thyroiditis is a medical disease that affects about 5% of the population. In cases of goitre, hashitoxicosis or associated differentiated thyroid cancer, surgical treatment is recommended. The aim of this study was to evaluate the indications for thyroidectomy in Hashimoto's thyroiditis, the frequency of coexistence of Hashimoto's thyroiditis and differentiated thyroid cancer, and the impact of Hashimoto's thyroiditis on the management of differentiated thyroid cancer. From January 1998 to May 2002, 344 patients underwent thyroidectomy in our department. Among 44 patients with HT, the authors carried out a retrospective comparative study of 33 patients with a cytological diagnosis of differentiated thyroid cancer (group A) and 11 patients with non-neoplastic conditions (group B). Surgical indications based on cytological findings and management characteristics were considered. The frequency of the association of Hashimoto's thyroiditis and differentiated thyroid cancer was 23.8% as compared to a 6.7% frequency of coexisting Hashimoto's thyroiditis and benign thyroid diseases (P = 0.000). The sensitivity of cytology in the diagnosis of papillary carcinoma in Hashimoto's thyroiditis was 92%. Cytological diagnosis of hyperplastic follicular and hyperplastic Hürthle cell nodules in Hashimoto's thyroiditis was impossible in some cases. Intraoperatively distinguishing between chronic lymph-node reactivity and tumour involvement was difficult, but the morbidity rate was not increased very much by Hashimoto's thyroiditis. In conclusion, an adequate follow up of patients with Hashimoto's thyroiditis may permit an early diagnosis of differentiated thyroid cancer and its appropriate management.

Adolescent↗
PubMed1990

Inhibition by immunoglobulin G of synthesis of thyroid hormone in thyroid cultures from hypothyroid patients with goitrous Hashimoto's thyroiditis.

Recently, thyroid microsomal antigen was identified as thyroid peroxidase, and thyroid microsomal antibody was found to inhibit thyroid peroxidase activity in vitro. We investigated the possibility that anti-microsomal antibody inhibits the iodination of tyrosine, in vivo. Immunoglobulin G with or without anti-microsomal antibody from hypothyroid patients with goitrous Hashimoto's thyroiditis inhibited thyroid hormone synthesis in cultured slices of normal human thyroid tissue. IgGs with anti-microsomal antibody inhibited 125I thyroidal uptake and thyroid hormone synthesis stimulated by TSH more than normal IgG did. However, the same results were obtained with IgGs without anti-microsomal antibody. This effect did not involve anti-microsomal antibody, anti-thyroglobulin antibody, TSH-binding inhibitor immunoglobulin, thyroid stimulation-blocking immunoglobulin, or the cAMP level of the thyroid tissue. The ratio of organic I to inorganic I with stimulation by TSH in slices incubated with IgG from hypothyroid patients with goitrous Hashimoto's thyroiditis or normal IgG was not significantly different, but was significantly higher in slices incubated with methylmercaptoimidazole. Therefore, IgG from hypothyroid patients with goitrous Hashimoto's thyroiditis mainly suppressed 125I thyroidal uptake, rather than inhibiting thyroid peroxidase activity. In addition, this IgG was present in the serum of 11 of the 12 hypothyroid patients with Hashimoto's thyroiditis studied. This IgG may be involved in the mechanism that causes hypothyroidism in some patients with goitrous Hashimoto's disease.

Adult↗
PubMed1990

A diminished adherence of blood lymphocytes of patients with thyroid autoimmune disease to high endothelial venules in the thyroid and the thyroid-draining lymph nodes.

The function of high endothelial venules (HEVs), present in the T-cell area of lymphoid tissue is to attract lymphocytes to secondary lymphoid organs ("homing"). In Graves' disease, sporadic goitre and lymphocytic thyroiditis HEVs develop in the thyroid. To study the "homing" of peripheral blood lymphocytes (PBL) of healthy individuals and thyroid patients to the thyroid area we studied the adherence of PBL of such individuals to HEVs present in Hashimoto's goitres and to HEVs in thyroid draining lymph nodes. A modification of the in vitro "homing assay" described by Stamper and Woodruff (J Exp Med 144: 823) was used. The number of PBL of patients with Graves' disease which adhered to thyroidal and thyroid-draining lymphnode HEVs was significantly (p less than or equal to 0.001, Wilcoxon test) less than that of healthy control PBL's; in the case of thyroid HEVs 12 (mean, sd 8, n = 18) patient lymphocytes adhered to 35 HEVs vs 19 (mean, sd 7, n = 16) healthy control lymphocytes; in the case of thyroid lymphnode HEVs 20 (mean, sd 12, n = 15) patient lymphocytes adhered vs 35 (mean, sd 9, n = 9) healthy control lymphocytes. PBL of a few sporadic goitre (n = 5) and atrophic lymphocytic thyroiditis (n = 2) patients also showed a diminished adherence to thyroidal HEVs. We also studied the homing capability of lymphocyte suspensions isolated from the thyroid glands of three Graves' disease patients; these infiltrated cells showed a normal adherence pattern to thyroidal HEVs. We favour the idea that the data should be explained by a redistribution of lymphocytes possessing "thyroid-specific-homing-receptors" from the circulation to the thyroid area in patients with thyroid autoimmune disease.

Adolescent↗
PubMed1996

Marked increases in cathepsin B and L activities distinguish papillary carcinoma of the thyroid from normal thyroid or thyroid with non-neoplastic disease.

Cathepsin B (CB) and cathepsin L (CL) are cysteine endopeptidases involved in the processing of thyroglobulin (Tg) in the normal thyroid. As thyroglobulin expression is frequently altered in thyroid carcinomas, we have analyzed 42 human thyroid tissues from 40 patients to study the effect of malignant transformation an the expression of these endopeptidases. Our samples included 18 cases of papillary carcinoma (of which 10 also had matched adjacent normal thyroid tissue), 6 cases of normal thyroid from autopsy patients, 1 case of follicular carcinoma, 2 cases of medullary carcinoma, 2 cases of follicular adenoma, 3 cases of Hashimoto's thyroiditis (HT) and 10 samples from 8 patients with multi-nodular goiter (MNG). Enzyme-specific activities were increased 15-fold for CB and 9-fold for CL in papillary carcinoma compared with normal adjacent thyroid tissue or normal thyroid from autopsies. CB mRNA content was also markedly increased in papillary carcinoma compared with normal thyroid, primarily due to elevated levels of the 2.2-kb CB mRNA transcript. In thyroids with nonneoplastic diseases, including MNG and HT, there was no significant increase in either CB or CL enzyme activities nor CB mRNA levels compared with normal thyroids from non-cancer cases. Immunohistochemical studies on papillary carcinomas revealed increased CB staining in papillary carcinoma cells, with prominent staining close to the basement membranes of many of the neoplastic cells. Our observations suggest that CB and CL enzyme activities are potentially useful new biochemical markers for distinguishing papillary carcinoma of the thyroid from non-neoplastic thyroid disease.

Adenocarcinoma, Follicular↗
PubMed2002

Differential expression of IgG Fc binding protein (FcgammaBP) in human normal thyroid tissue, thyroid adenomas and thyroid carcinomas.

The genetic events involved in thyroid carcinogenesis are still incompletely understood. Several rearrangements and mutations of oncogenes have been implicated in the development of thyroid papillary carcinomas, follicular adenomas and carcinomas. However, none of these molecular alterations is suitable either as a general marker for the diagnosis of thyroid carcinomas or to differentiate between thyroid follicular adenomas and carcinomas. In order to identify new genes with altered expression which could serve as such markers, we analyzed RNA from thyroid tumor and normal tissue using a novel technique called restriction-mediated differential display. Several differentially expressed genes were identified, including the gene for IgG Fc binding protein (FcgammaBP). Differential expression of FcgammaBP was confirmed by quantitative real-time RT-PCR. Our experiments showed that IgG Fc binding protein (FcgammaBP) is differentially expressed in normal thyroid tissue, thyroid adenomas and thyroid carcinomas. While the FcgammaBP gene is constitutively expressed in normal thyroid tissue, its expression is significantly increased in follicular thyroid adenomas and significantly decreased in papillary and follicular thyroid carcinomas. Thus, measurement of the expression levels of FcgammaBP in thyroid biopsies might help to make the otherwise difficult distinction between a thyroid follicular adenoma and a follicular carcinoma.

Adenoma↗
PubMed1993

Autoimmune thyroiditis induced in mice depleted of particular T cell subsets. Characterization of thyroiditis-inducing T cell lines and clones derived from thyroid lesions.

We have previously shown that autoimmune thyroiditis spontaneously develops in T cell-depleted (C57BL/6xC3H/He)F1 mice after adoptive transfer of syngeneic lymphoid cells that have been depleted of CD5bright T lymphocytes. This mouse model was considered to be an instructive model for Hashimoto's thyroiditis in humans, and suggested that CD5dull CD4+ autoreactive T cells are not deleted in normal lymphoid cell populations and induce thyroiditis after elimination of regulatory T cell subsets. In our study, we have established thyroid-derived T cell lines and clones by culturing thyroid-infiltrating lymphocytes with thyroid epithelial cells and syngeneic feeder cells in the presence of exogenous IL-2. Both CD4+ T cells and CD8+ T cells were identified and their CD5 expression was dull or negative. In our report, we focused on CD4+ T cells. Four CD4+ T cell lines and 19 clones were generated and characterized. CD4+ T cell clones derived from F1 hybrid (H-2b/k) mice responded to thyroid Ag in the context of not only class II MHC molecules from both parental strains (I-Ak or I-Ab), but also F1 unique MHC molecules. Thyroglobulin (Tg) was demonstrated to be a major autoantigen of the thyroid for T cell responses, and at least two epitopes of Tg were suggested to be recognized by T cell clones. An additional undefined thyroid component other than Tg was recognized by some T cell clones. Thyroid-derived T cells were all TCR-alpha beta+. Five types of V beta usage (V beta 2, 4, 8.3, 14, and an undefined V beta) were found in CD4+ T cells. Finally, the thyroid lesions could be transferred to syngeneic mice by five distinct groups of CD4+ T cell clones, which were distinguished on the basis of their Ag specificity, MHC restriction, and TCRV beta usage. The considerable heterogeneity of TCRV beta usage of thyroiditis-inducing T cell clones in this study may be attributed to the multiple patterns of their recognition of the thyroid autoantigens. These findings provide important implications for further understanding of organ-specific autoimmune processes induced by depletion of regulatory T cell subsets.

Animals↗