Induction of experimental autoimmune thyroiditis in mice with in vitro activated splenic T cells

Braley‐Mullen, Helen; Johnson, Michael W.; Sharp, Gordon C.; Kyriakos, Michael

doi:10.1016/0008-8749(85)90394-6

Cited by 90 publications

(78 citation statements)

References 17 publications

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“…Donor mice were injected intravenously twice at 10-day intervals with 150 g MTg, prepared as described previously, 3 and with 15 g lipopolysaccharide (Sigma-Aldrich, St. Louis, MO). One week later, donor spleen cells were activated in vitro with 25 g/mL MTg and 5 ng/mL IL-12 (PeproTech, Rocky Hill, NJ) or 20 ng/mL IL-23 (eBioscience) as described previously.…”

Section: Induction Of G-eatmentioning

confidence: 99%

“…[3][4][5][6][7] Serum dilution is reported in Table 1. Normal mouse serum used at the same dilutions always gave an optical density value of OD Ͻ 0.05.…”

Section: Determination Of Anti-mtg Autoantibody Responsesmentioning

confidence: 99%

“…179,No. 3 blocking, frozen thyroid sections were incubated with rat anti-IFN-␥ (XMG1.2; ATCC), rabbit anti-TNF-␣ (Santa Cruz Biotechnology, Santa Cruz, CA), goat anti-IL-10 (Santa Cruz Biotechnology), rabbit anti-IL-5 (Santa Cruz Biotechnology), rat anti-CD4 (GK1.5; ATCC), and rat anti-CD8 (53.6; ATCC) antibodies for 60 minutes at room temperature.…”

Section: Ihcmentioning

confidence: 99%

“…Transgenic FLIP was expressed on CD4 ؉ Experimental autoimmune thyroiditis (EAT) is a chronic inflammatory autoimmune disease that can be induced in genetically susceptible strains of mice by injecting mouse thyroglobulin (MTg) and adjuvant 1,2 or by transferring MTg-primed donor spleen cells activated with MTg in vitro. 2,3 A severe granulomatous form of EAT (G-EAT) is induced when MTg-sensitized donor spleen cells are activated in vitro with MTg and IL-12 4,5 or with MTg and IL-23 (unpublished data). Thyroid lesions in G-EAT are characterized by infiltration of inflammatory cells and destruction of thyroid epithelial cells.…”

mentioning

confidence: 99%

“…[3][4][5][6][7] Thyroid lesions reach maximal severity 20 days after cell transfer, and inflammation either resolves or progresses to fibrosis at day 50 to day 60, depending on the extent of damage at day 20. [3][4][5][6][7] DBA/1 recipients typically develop very severe thyroid lesions (5ϩ severity score) by day 20, with few or no remaining intact follicles, and inflammation and fibrosis persist 60 days after cell transfer. 4 -7 CBA/J recipients also develop very severe G-EAT, but there are usually some intact thyroid follicles, less neutrophil infiltration, and less fibrosis at day 20, compared with lesions in DBA/1 mice.…”

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confidence: 99%

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Effect of Transgenic Overexpression of FLIP on Lymphocytes on Development and Resolution of Experimental Autoimmune Thyroiditis

Fang

Sharp

Braley‐Mullen

2011

The American Journal of Pathology

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In our previous studies, resolution of granulomatous experimental autoimmune thyroiditis (G-EAT) was promoted when thyroid epithelial cells were protected from Fas-mediated apoptosis due to transgenic overexpression of FLIP. We hypothesized that if FLIP were overexpressed on lymphocytes, CD4 ؉ effector cells would be protected from Fas-mediated apoptosis, and resolution would be delayed. To test this hypothesis, we generated transgenic (

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Section: Induction Of G-eatmentioning

confidence: 99%

“…[3][4][5][6][7] Serum dilution is reported in Table 1. Normal mouse serum used at the same dilutions always gave an optical density value of OD Ͻ 0.05.…”

Section: Determination Of Anti-mtg Autoantibody Responsesmentioning

confidence: 99%

Section: Ihcmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Effect of Transgenic Overexpression of FLIP on Lymphocytes on Development and Resolution of Experimental Autoimmune Thyroiditis

Fang

Sharp

Braley‐Mullen

2011

The American Journal of Pathology

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The involvement of IL-12 in murine experimentally induced autoimmune thyroid disease

et al. 1999

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Experimental autoimmune thyroid disease (EAT) can be induced experimentally in mice following immunization with mouse thyroglobulin (mTg) and the adjuvants lipopolysaccharide (LPS) or complete Freund's adjuvant (CFA). EAT can also be transferred to naive recipients by CD4 + T cells from mTg-primed mice. Here we demonstrate a role for IL-12 in the development of EAT by the ability of neutralizing antibody to IL-12 to reduce disease severity and by the lack of significant levels of thyroid infiltration in IL-12p40-deficient mice following immunization with mTg and CFA. A single injection of 300 ng IL-12 at the time of initial immunization with mTg and LPS was able to increase the degree of thyroid infiltration. These data are all consistent with EAT being a Th1-mediated disease. Conversely, however, administration of IL-12 over a prolonged period markedly inhibited the induction of EAT by mTg and CFA and, if given to recipients, inhibited the transfer of EAT by mTg-primed lymph node cells. The development of an autoantibody response to mTg was also inhibited when IL-12 was administered throughout the experimental period, suggesting that sustained exposure to IL-12 can be immunosuppressive.

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A critical role for TRAIL in resolution of granulomatous experimental autoimmune thyroiditis

Fang

Sharp

Yagita

et al. 2008

The Journal of Pathology

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Granulomatous experimental autoimmune thyroiditis (G-EAT) is induced by mouse thyroglobulin (MTG)-sensitized splenocytes activated in vitro with MTG and IL-12. Thyroid lesions reach maximal severity 20 days after cell transfer, and usually resolve or progress to fibrosis by day 60 depending on the extent of thyroid damage at day 20. Our previous studies indicated that neutralization of TNF-α or FasL had no effect on G-EAT induction, but neutralization of TNF-α promoted, while neutralization of FasL inhibited G-EAT resolution. TNF-related apoptosisinducing ligand (TRAIL) is a member of the TNF superfamily. This study was undertaken to define the role of endogenous TRAIL in G-EAT development and/or resolution. Neutralization of endogenous TRAIL had little effect on G-EAT induction, but significantly inhibited G-EAT resolution and increased thyroid fibrosis. This correlated with higher expression of proinflammatory cytokines and preferential expression of the pro-apoptotic molecule TRAIL, and anti-apoptotic molecules FLIP and Bcl-xL on inflammatory cells in thyroids of anti-TRAILtreated recipients. Furthermore, CD4+ T cells outnumbered CD8+ T cells in thyroids of anti-TRAIL-treated recipients. The results suggest that endogenous TRAIL is not required for G-EAT development in recipients, but is critical for G-EAT resolution. Endogenous TRAIL might promote resolution, at least in part, through modulation of the balance between pro-and antiinflammatory cytokines, and the expression pattern of pro-and anti-apoptotic molecules of thyroid epithelial cells (TEC) and inflammatory cells.

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Induction of experimental autoimmune thyroiditis in mice with in vitro activated splenic T cells

Cited by 90 publications

References 17 publications

Effect of Transgenic Overexpression of FLIP on Lymphocytes on Development and Resolution of Experimental Autoimmune Thyroiditis

Effect of Transgenic Overexpression of FLIP on Lymphocytes on Development and Resolution of Experimental Autoimmune Thyroiditis

The involvement of IL-12 in murine experimentally induced autoimmune thyroid disease

A critical role for TRAIL in resolution of granulomatous experimental autoimmune thyroiditis

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