Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin 2 (IL-2) is a lymphokine that may disrupt immunological self-tolerance. While being incapable of interfering with intrathymic or peripheral clonal deletion, IL-2 may overcome functional antigen unresponsiveness in anergic T lymphocytes. Anergy of T helper cells of the inflammatory phenotype implies selective silencing of the transcription of the IL-2 gene and thus precludes autocrine IL-2/IL-2 receptor (IL-2R) mediated growth, as well as delivery of help to other T cells or B lymphocytes. Thus, IL-2 serves as a servomodulator regulating post-deletional self-tolerance. IL-2-producing and IL-2-receptive cells are present in a variety of autoimmune lesions, including spontaneous autoimmune thyroiditis developing in the Obese strain (OS) of chickens, in Hashimoto's struma lymphomatosa, and in Graves' disease. Whereas the OS is characterized by a hyperinducibility of the IL-2/IL-2R system that predisposes to the development of severe thyroid infiltration, the state of the IL-2/IL-R system in circulating lymphocytes of patients developing thyroid autoimmunity, or at risk of doing so, remains to be defined. The most frequent autoimmune side-effect of IL-2 treatment concerns the thyroid gland. IL-2 induces a lymphoid thyroiditis leading to primary hypothyroidism, especially in those patients that have pre-treatment antithyroid autoantibodies. The hypothesis is extrapolated that IL-2 induces autoimmune disease in those patients that bear undeleted thyroid-specific T cells, and in which the lack of manifest thyroiditis relies upon peripheral, post-deletional tolerance.
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PMID:The role of interleukin 2 in the development of autoimmune thyroiditis. 148 52

We measured soluble interleukin 2 receptor, a part of the Tac protein (p55), in peripheral blood to study the immunological condition of the T cell in autoimmune thyroid disease. In 26 patients with untreated Graves' disease and 7 hyperthyroid patients with Hashimoto's thyroiditis, the mean levels of soluble IL-2 receptor were both significantly higher than in normal controls (1497 +/- 649 (mean +/- SD), 641 +/- 137 vs 221 +/- 63 10(3) U/l, p less than 0.001). There was good correlation between soluble IL-2 receptor levels and blood thyroxine levels (r = 0.684, p less than 0.001) in patients with untreated Graves' disease, but no correlation of soluble IL-2 receptor with TSH-inhibitory immunoglobulins, TS-ab, thyroidal autoantibodies to thyroglobulin and thyroidal microsomal antigen was found. We thought that the level of soluble IL-2 receptor is not dependent only on immunological conditions, but also on thyroid hormone status. When T3 was administered to subjects in remission from Graves' disease and in normal controls, the soluble IL-2 receptor levels significantly increased. Moreover, the mean level of soluble IL-2 receptor in patients with toxic multinodular goitre was also significantly higher than in normal controls (411 +/- 148 vs 221 +/- 63 10(3)U/l, p less than 0.05). We conclude that the soluble IL-2 receptor levels are higher in sera of subjects with elevated levels of thyroid hormone.
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PMID:Increased soluble interleukin 2 receptor levels in autoimmune thyroid disease. 168 85

Because of interest in IL-2, and IL-2-activated killer cell-induced hypothyroidism in humans, we attempted to study an in vitro system that might prove to illuminate this disorder. We have thus studied interleukin 2 (IL-2--0, 12.5, 25, or 50 U/mL) activated killer cell-mediated autologous thyrocyte lysis, as well as cytotoxic activity in IL-2-stimulated mononuclear cell supernatants in 7 patients with autoimmune thyroid disease (2 Graves' disease and 5 Hashimoto's thyroiditis) using the 51Cr release assay. Controls included 14 patients with nonautoimmune thyroid disease (3 nontoxic goiter, 8 follicular thyroid adenoma, 2 papillary thyroid carcinoma, and 1 medullary carcinoma of the thyroid). Soluble IL-2 receptor (sIL-2R) in supernatants of peripheral mononuclear cells stimulated by IL-2 from these patients also was measured. Whereas in the control preparations, IL-2-activated killer cell activity was increased in a dose-dependent fashion relative to the IL-2 concentration, as well as to the effector cell/target cell ratio, in preparations from patients with autoimmune thyroid disease, this activity was not elevated as the IL-2 concentration was increased. The susceptibility of thyrocytes to the lytic effect of IL-2-activated killer cells was higher in controls than that in autoimmune thyroid disease (at concentrations of IL-2 of 0, 12.5, 25, and 50 U/mL) (p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin 2-activated killer cells do not mediate autologous thyrocyte lysis in autoimmune thyroid disease in vitro. 182 61

In order to clarify the autoimmune mechanisms of anti-Tg antibody (anti-TgAb) in autoimmune thyroid disease (AITD), a series of examinations were conducted in patients with Graves' disease (n = 59), Hashimoto's thyroiditis (n = 63) and healthy controls (n = 38). Our findings can be summarized as follows: 1) The distribution of anti-TgAb was measured by IgG subclass ELISA. IgG1 and/or IgG4 antibodies formed the major anti-Tg response, but in some patients, IgG2 anti-Tg tend to be the predominant response. We used ELISA to determine an IgG1 anti-Tg bound to Tg that had already interacted with IgG2 Tg-antibody (and vice versa). The results substantiated the view that TgAb of a different IgG subclass interact with different epitopes on Tg. 2) Human antiidiotypic (anti-Id) antibodies to anti-Tg antibody occur spontaneously in the AITD. These anti-Id antibodies can be divided into two categories based on properties of their binding sites. One type acts like a 'internal image' of Tg antigen which shown Ab2 beta activity. Another type has Ab2 alpha activity that recognizes Id determinants in the framework region common among anti-Tg antibody. 3) We also examined the competitive binding assay between TgAb and TgAb F(ab')2 fragments, and demonstrated differences in the TgAb repertoires between patients. 4) Soluble IL-2 receptor (IL-2R) of patients significantly increased as compared with normal subjects and IL-2R values in GD were higher than those in HT (p < 0.001). Therefore, IL-2R is regarded as a useful marker for disease activity.
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PMID:Studies on autoimmune mechanisms of thyroglobulin autoantibody in autoimmune thyroid disease. 801 70

Hyperthyroidism in Graves' disease is caused by thyroid-stimulating autoantibodies to the TSH receptor (TSHR), whereas hypothyroidism in Hashimoto's thyroiditis is associated with thyroid peroxidase and thyroglobulin autoantibodies. In some Graves' patients, thyroiditis becomes sufficiently extensive to cure the hyperthyroidism with resultant hypothyroidism. Factors determining the balance between these two diseases, the commonest organ-specific autoimmune diseases affecting humans, are unknown. Serendipitous findings in transgenic BALB/c mice, with the human TSHR A-subunit targeted to the thyroid, shed light on this relationship. Of three transgenic lines, two expressed high levels and one expressed low intrathyroidal A-subunit levels (Hi- and Lo-transgenics, respectively). Transgenics and wild-type littermates were depleted of T regulatory cells (Treg) using antibodies to CD25 (CD4(+) T cells) or CD122 (CD8(+) T cells) before TSHR-adenovirus immunization. Regardless of Treg depletion, high-expressor transgenics remained tolerant to A-subunit-adenovirus immunization (no TSHR antibodies and no hyperthyroidism). Tolerance was broken in low-transgenics, although TSHR antibody levels were lower than in wild-type littermates and no mice became hyperthyroid. Treg depletion before immunization did not significantly alter the TSHR antibody response. However, Treg depletion (particularly CD25) induced thyroid lymphocytic infiltrates in Lo-transgenics with transient or permanent hypothyroidism (low T(4), elevated TSH). Neither thyroid lymphocytic infiltration nor hypothyroidism developed in similarly treated wild-type littermates. Remarkably, lymphocytic infiltration was associated with intermolecular spreading of the TSHR antibody response to other self thyroid antigens, murine thyroid peroxidase and thyroglobulin. These data suggest a role for Treg in the natural progression of hyperthyroid Graves' disease to Hashimoto's thyroiditis and hypothyroidism in humans.
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PMID:The link between Graves' disease and Hashimoto's thyroiditis: a role for regulatory T cells. 1782 63