IL-12 Prevents Tolerance Induction with Mouse Thyroglobulin by Priming Pathogenic T Cells in Experimental Autoimmune Thyroiditis: Role of IFN-γ and the Costimulatory Molecules CD40L and CD28

2001 ◽  
Vol 208 (1) ◽  
pp. 52-61 ◽  
Author(s):  
Wei Zhang ◽  
Jeffrey C. Flynn ◽  
Yi-chi M. Kong
Keyword(s):  
T Cells ◽  
Autoimmune Thyroiditis ◽  
Tolerance Induction ◽  
Costimulatory Molecules ◽  
Experimental Autoimmune Thyroiditis ◽  
Ifn Γ ◽  
Experimental Autoimmune

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 TGF-β inhibitor Smad7 regulates dendritic cell-induced autoimmunity

2017 ◽  
Vol 114 (8) ◽  
pp. E1480-E1489 ◽  
Author(s):  
Dominika Lukas ◽  
Nir Yogev ◽  
Junda M. Kel ◽  
Tommy Regen ◽  
Ilgiz A. Mufazalov ◽  
...  
Keyword(s):  
T Cells ◽  
Tolerance Induction ◽  
Autoimmune Encephalomyelitis ◽  
Elevated Expression ◽  
The Central Nervous System ◽  
Smad7 Expression ◽  
Ifn Γ ◽  
Tolerogenic Function ◽  
Anti Inflammatory Cytokine ◽  
Experimental Autoimmune

TGF-β is an anti-inflammatory cytokine whose signaling is negatively controlled by Smad7. Previously, we established a role for Smad7 in the generation of autoreactive T cells; however, the function of Smad7 in dendritic cells (DCs) remains elusive. Here, we demonstrate that DC-specific Smad7 deficiency resulted in elevated expression of the transcription factors Batf3 and IRF8, leading to increased frequencies of CD8+CD103+DCs in the spleen. Furthermore, Smad7-deficient DCs expressed higher levels of indoleamine 2,3-dioxygenase (IDO), an enzyme associated with tolerance induction. Mice devoid of Smad7 specifically in DCs are resistant to the development of experimental autoimmune encephalomyelitis (EAE) as a result of an increase of protective regulatory T cells (Tregs) and reduction of encephalitogenic effector T cells in the central nervous system. In agreement, inhibition of IDO activity or depletion of Tregs restored disease susceptibility. Intriguingly, when Smad7-deficient DCs also lacked the IFN-γ receptor, the mice regained susceptibility to EAE, demonstrating that IFN-γ signaling in DCs mediates their tolerogenic function. Our data indicate that Smad7 expression governs splenic DC subset differentiation and is critical for the promotion of their efficient function in immunity.

The effects of a monoclonal antibody to interferon-γ on experimental autoimmune thyroiditis (EAT): prevention of disease and decrease of EAT-specific T cells

1993 ◽  
Vol 23 (1) ◽  
pp. 275-278 ◽  
Author(s):  
Haiwen Tang ◽  
Karine Mignon-Godefroy ◽  
Pier Luigi Meroni ◽  
Gianni Garotta ◽  
Jeannine Charreire ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
Autoimmune Thyroiditis ◽  
Interferon Γ ◽  
Experimental Autoimmune Thyroiditis ◽  
Experimental Autoimmune
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