scholarly journals THE ROLE OF MYCOBACTERIA AND THE EFFECT OF PROTEOLYTIC DEGRADATION OF THYROGLOBULIN ON THE PRODUCTION OF AUTOIMMUNE THYROIDITIS

1969 ◽  
Vol 130 (2) ◽  
pp. 243-262 ◽  
Author(s):  
W. O. Weigle ◽  
Gloria J. High ◽  
R. M. Nakamura
Keyword(s):  
Autoimmune Thyroiditis ◽  
Proteolytic Enzymes ◽  
Ion Concentration ◽  
Experimental Autoimmune Thyroiditis ◽  
Hydrogen Ion Concentration ◽  
Initial Event ◽  
Local Areas ◽  
Experimental Autoimmune

Data are presented which suggest that the initial event involved in experimental autoimmune thyroiditis following injection of rabbits with homologous thyroglobulin in complete Freund's adjuvant is alteration of the thyroglobulin. Alteration of the thyroglobulin does not occur during incorporation into the adjuvant or in vitro storage in the adjuvant, and the mycobacteria in the adjuvant have no direct effect on the thyroglobulin. Most likely, the alteration results from an increase in hydrogen ion concentration within cells or local areas in the granuloma and the subsequent action of proteolytic enzymes. These conditions are probably established in the granuloma as the result of neutrophilic response to the mycobacteria in the adjuvant. Rabbits injected with aqueous preparations of homologous thyroglobulin partially degraded in vitro with pepsin at acid pH produced antibody to native thyroglobulin and developed thyroiditis. Most of these rabbits responded to a subsequent injection of native thyroglobulin given 1 month later.

scholarly journals Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Inhibits Experimental Autoimmune Thyroiditis by the Expansion of CD4+CD25+ Regulatory T Cells

Endocrinology ◽  
2008 ◽  
Vol 150 (4) ◽  
pp. 2000-2007 ◽  
Author(s):  
Su He Wang ◽  
Gwo-Hsiao Chen ◽  
Yongyi Fan ◽  
Mary Van Antwerp ◽  
James R. Baker
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Autoimmune Thyroiditis ◽  
Rabbit Model ◽  
Experimental Autoimmune Thyroiditis ◽  
Autoimmune Encephalomyelitis ◽  
Necrosis Factor ◽  
Experimental Autoimmune

There have been several reports that TNF-related apoptosis-inducing ligand (TRAIL) has the ability to suppress the development of experimental autoimmune diseases, including a mouse model of experimental autoimmune encephalomyelitis, a rabbit model of rheumatoid arthritis, type 1 diabetes mellitus, in mice and experimental autoimmune thyroiditis (EAT) in mice. However, the mechanism underlying TRAIL effect is not well defined. In the present study, we specifically examined TRAIL effects on CD4+CD25+ regulatory T cells. CD4+CD25+ T cells prepared from mouse thyroglobulin (mTg)-immunized CBA/J mice proliferate in the presence of TRAIL and dendritic cells in vitro. These CD4+CD25+ T cells included both CD4+CD25+CD45RBLow (regulatory) and CD4+CD25+CD45RBHigh (effector) T cells. Our results demonstrated that mTg-immunized mice treated with TRAIL showed significant increases in the number of CD4+CD25+CD45RBLow T cells compared with mice immunized with mTg alone. CD4+CD25+CD45RBLow T cells expressed much higher levels of the forkhead family transcription factor, IL-10, and TGFβ1 than CD4+CD25+CD45RBHigh T cells, and these cells can completely suppress the proliferation of the mTg-primed splenocytes in lower concentrations than the unfractionated CD4+CD25+ T cells. Furthermore, transfer of these cells into CBA/J mice prior to mTg-primed splenocyte injection could markedly reduce the frequency and severity of EAT development. CD4+CD25+CD45RBLow T cells were more effective at suppressing histological thyroiditis than unfractionated cells. These results indicated that TRAIL can increase the number of mTg-specific CD4+CD25+CD45RBLow T cells, inhibiting autoimmune responses and preventing the progression of EAT. These findings reveal a novel mechanism by which TRAIL could inhibit autoimmune disease.

scholarly journals Death Ligand Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Inhibits Experimental Autoimmune Thyroiditis

Endocrinology ◽  
2005 ◽  
Vol 146 (11) ◽  
pp. 4721-4726 ◽  
Author(s):  
Su He Wang ◽  
Zhengyi Cao ◽  
Julie M. Wolf ◽  
Mary Van Antwerp ◽  
James R. Baker
Keyword(s):  
Autoimmune Thyroiditis ◽  
T Helper ◽  
Mononuclear Cell Infiltration ◽  
T Helper 1 ◽  
Experimental Autoimmune Thyroiditis ◽  
Cell Responses ◽  
Control Protein ◽  
Necrosis Factor ◽  
Experimental Autoimmune

The role of TNF-related apoptosis-inducing ligand (TRAIL) in autoimmune thyroiditis is unclear. We used experimental autoimmune thyroiditis to clarify the contribution of TRAIL to the development of autoimmune thyroiditis. CBA/J mice were immunized with murine thyroglobulin, and spleen cells from these mice were subsequently injected into irradiated recipient CBA/J mice. One week later, the recipient mice were treated with recombinant TRAIL or a control protein. Compared with control animals, TRAIL-treated mice developed a milder form of the disease with a significant decrease in mononuclear cell infiltration in the thyroid and less thyroid follicular destruction. Furthermore, the number of apoptotic thyrocytes and also thyroglobulin-specific T helper-1 cell responses in TRAIL-treated mice was lower than that in the control animals. This study suggests that exogenous TRAIL suppresses the development of autoimmune thyroiditis via altering the function of cells involved in the immune response. These findings may contribute toward a novel treatment autoimmune thyroiditis.

Unique role of thyroxine in T cell recognition of a pathogenic peptide in experimental autoimmune thyroiditis

1996 ◽  
Vol 26 (4) ◽  
pp. 768-772 ◽  
Author(s):  
Kim I. Dawe ◽  
Patricia R. Hutchings ◽  
Mario Geysen ◽  
Brian R. Champion ◽  
Anne Cooke ◽  
...  
Keyword(s):  
T Cell ◽  
Autoimmune Thyroiditis ◽  
Cell Recognition ◽  
Experimental Autoimmune Thyroiditis ◽  
Unique Role ◽  
T Cell Recognition ◽  
Experimental Autoimmune

scholarly journals Cultured Murine Thyroid Epithelial Cells Expressing Transgenic Fas-Associated Death Domain-Like Interleukin-1β Converting Enzyme Inhibitory Protein Are Protected from Fas-Mediated Apoptosis

Endocrinology ◽  
2008 ◽  
Vol 149 (7) ◽  
pp. 3321-3329 ◽  
Author(s):  
Yujiang Fang ◽  
Helen Braley-Mullen
Keyword(s):  
Epithelial Cells ◽  
Autoimmune Thyroiditis ◽  
Death Domain ◽  
Converting Enzyme ◽  
Experimental Autoimmune Thyroiditis ◽  
Inhibitory Protein ◽  
Rna Transfection ◽  
Experimental Autoimmune

The antiapoptotic molecule Fas-associated death domain-like IL-1β-converting enzyme inhibitory protein (FLIP) inhibits Fas-mediated apoptosis by blocking activation of caspase-8. We previously showed that expression of transgenic FLIP on thyroid epithelial cells (TECs) of DBA/1 and CBA/J mice promoted earlier resolution of granulomatous experimental autoimmune thyroiditis in vivo. This study was undertaken to directly determine whether transgenic FLIP expressed on cultured TECs can protect TECs from Fas-mediated apoptosis in vitro. The results indicate that cultured TECs from DBA/1 and CBA/J mice can be sensitized in vitro by interferon-γ and TNF-α to undergo Fas-mediated apoptosis. Transgenic overexpression of FLIP protected cultured TECs of FLIP transgene (Tg)+ DBA/1 and CBA/J mice from Fas-mediated apoptosis, and FLIP small interfering RNA transfection of cultured TECs of FLIP Tg+ DBA/1 and CBA/J mice abolished the protective effect. These in vitro results are consistent with our previous in vivo studies using DBA/1 and CBA/J FLIP Tg+ mice and provide direct support for the hypothesis that transgenic expression of FLIP promotes resolution of granulomatous experimental autoimmune thyroiditis by protecting TECs from apoptosis.

The accumulation of [35S]methimazole by human and rat lymphocytes

1983 ◽  
Vol 102 (1) ◽  
pp. 68-70 ◽  
Author(s):  
G. S. Shewring ◽  
J. H. Lazarus
Keyword(s):  
Antibody Production ◽  
Autoimmune Thyroiditis ◽  
Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Graves Disease ◽  
Experimental Autoimmune Thyroiditis ◽  
Rat Lymphocytes ◽  
Immunosuppressive Action ◽  
Experimental Autoimmune

Abstract. The accumulation of 35S labelled methimazole (MMI) was examined in lymphocytes. No uptake of label was found in peripheral blood lymphocytes (PBL) from normal control subjects after in vitro incubation with the drug. Following administration of [35S]MMI to patients with Graves' hyperthyroidism PBL cell to plasma (C/P) 35S activity was greater than 1 in 4 of 11 patients and only in 1 of 7 other patients undergoing thyroidectomy. Thyroid lymphocytes from 2 of these patients showed some accumulation of activity. Following administration of [35S]MMI to normal rats C/P 35S ratios ranged from 1–5.6 but no 35S accumulation was found in PBL or thyroid lymphocytes from August strain rats in which experimental autoimmune thyroiditis had been produced. It is concluded that there is minimal, if any, significant accumulation of MMI in lymphocytes of patients with Graves' disease. The immunosuppressive action of MMI on lymphocyte antibody production must therefore by indirect.

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