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

Direct multi-colour flow cytometric analysis was employed in patients with Graves' disease (n = 10) to determine the immunophenotype in peripheral blood lymphocytes (PBL) at the time of diagnosis without treatment (PBLw) and prior to operation (PBLp) and in thyroid-derived lymphocytes (TL). Additionally, the secretion of anti-thyroperoxidase antibodies (anti-TPO) was measured during culture of isolated peripheral or thyroid-derived B cells. Among TL from patients with high serum levels of anti-TPO (6/10) a significantly (p < 0.01) higher percentage of B cells were detected compared to PBLp (TL: 21.7 +/- 7.2%; PBLp: 13.2 +/- 4.5%). Enriched thyroid-derived B cells only from these patients also showed high spontaneous anti-TPO secretion during culture. The difference between peripheral and thyroid-derived natural killer (NK) cells was highly significant (p < 0.001; TL: 5.6 +/- 6.3%; PBLp: 13.6 +/- 5.5%). Two patients were found with a higher number of NK cells within TL. These patients were among those who had a low number of B cells infiltrating the thyroid gland. Regarding the expression of several other differentiation antigens, i.e. CD4 and CD8, gamma/delta TCR bearing T cells and CD45R0 on CD4+ T cells as a marker for memory cells, on TL no differences could be detected between patients with or without anti-TPO. In TL 31.5 +/- 7.7% of CD3- cells expressed the HLA-DR antigen (vs. 6.1 +/- 2.4% in PBLp; p < 0.001). Half of these cells simultaneously expressed the activation antigen CD69. Surprisingly, the number of CD3+ TL bearing the IL-2 receptor (CD25) and transferrin receptor (CD71) was not increased. Taken together, the proportional distribution of B and NK cells within the thyroid correlates with the anti-TPO secretion in vivo and in vitro, suggesting different immune response regulation processes of TL.
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PMID:Different immunophenotype and autoantibody production by peripheral blood and thyroid-derived lymphocytes in patients with Graves' disease. 875 May 71

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