Transgenic Lewis rats overexpressing the proteolipid protein gene: myelin degeneration and its effect on T cell-mediated experimental autoimmune encephalomyelitis

1999 ◽  
Vol 97 (6) ◽  
pp. 595-606 ◽  
Author(s):  
M. Bradl ◽  
J. Bauer ◽  
Takayuki Inomata ◽  
Jürgen Zielasek ◽  
Klaus-Armin Nave ◽  
...  
Keyword(s):  
T Cell ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Protein Gene ◽  
Proteolipid Protein ◽  
Autoimmune Encephalomyelitis ◽  
Lewis Rats ◽  
Experimental Autoimmune

scholarly journals Priming of Myelin-Specific T Cells in the Absence of Dendritic Cells Results in Accelerated Development of Experimental Autoimmune Encephalomyelitis

2020 ◽  
Author(s):  
Thaiphi Luu ◽  
Julie F. Cheung ◽  
Hanspeter Waldner
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Experimental Autoimmune Encephalomyelitis ◽  
T Cell Responses ◽  
Proteolipid Protein ◽  
Cell Receptor ◽  
Autoimmune Encephalomyelitis ◽  
Cell Responses ◽  
Experimental Autoimmune

AbstractExperimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), is predominantly mediated by pro-inflammatory CD4+ T cell responses to CNS antigens, including myelin proteolipid protein (PLP). Dendritic cells (DCs) are considered critical for inducing T cell responses against infectious agents, but the importance of DCs in priming self-reactive CD4+ T cells in autoimmune disease such as MS has been unclear.To determine the requirement of DCs in PLP-specific CD4+ T cell responses and EAE, we genetically deleted CD11c+ DCs in PLP T cell receptor (TCR) transgenic SJL mice constitutively. DC deficiency did not impair the development, selection or the pathogenic function of PLP-specific CD4+ T cells in these mice, and resulted in accelerated spontaneous EAE compared to DC sufficient controls. In addition, using a genetic approach to ablate DCs conditionally in SJL mice, we show that CD11c+ DCs were dispensable for presenting exogenous or endogenous myelin antigen to PLP-specific T cells and for promoting pro-inflammatory T cell responses and severe EAE. Our findings demonstrate that constitutive or conditional ablation of CD11c+ DCs diminished self-tolerance to PLP autoantigen. They further show that in the absence of DCs, non-DCs can efficiently present CNS myelin antigens such as PLP to self-reactive T cells, resulting in accelerated onset of spontaneous or induced EAE.

scholarly journals Prevention of experimental autoimmune encephalomyelitis in Lewis rats by a novel fungal source of γ-linolenic acid

1995 ◽  
Vol 74 (5) ◽  
pp. 701-715 ◽  
Author(s):  
L. S. Harbige ◽  
N. Yeatman ◽  
S. Amor ◽  
M. A. Crawford
Keyword(s):  
Body Weight ◽  
Linoleic Acid ◽  
T Cell ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Linolenic Acid ◽  
Safflower Seed ◽  
Con A ◽  
Autoimmune Encephalomyelitis ◽  
Lewis Rats ◽  
Experimental Autoimmune

The effects of oral administration of linoleic- and γ-inolenic-acid-rich oils on the clinical and histopathological manifestations of experimental autoimmune encephalomyelitis (EAE) were investigated in Lewis rats 7 d post-inoculation. γ-Linolenic-acid-rich fungal (Mucor javanicus) oil at 500 mg/kg body weight abrogated clinical and histological signs of EAE although at doses of 200 and 1000 mg/kg body weight it was only effective in delaying the onset of clinical disease. Linoleic-acid-rich safflower-seed (Carthamus tinctorius) oil at 500, 750 and 1000 mg/kg body weight decreased the severity of clinical EAE. disease in a dose-dependent manner. The effects in healthy animals of orally administered γ-linolenic-acid-rich fungal oil (500 mg/kg body weight) and linoleic-acid-rich safflower-seed oil (1000 mg/kg body weight) on splenic lymphocyte proliferative responses to the T-cell mitogen concanavalin-A (Con A), membrane fatty acid composition and lymphocyte sub-sets were also studied. Both treatments enhanced the T-cell proliferative response to Con A. There was no significant effect on the proportion of splenic CD8+ or CD4+ lymphocytes. Compositional studies on splenic phosphoglyceride fatty acids of oil-treated animals suggest the above responses were associated with increases in spleen dihomo-γ-linolenic and arachidonic acids.

scholarly journals Priming of myelin-specific T cells in the absence of dendritic cells results in accelerated development of Experimental Autoimmune Encephalomyelitis

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250340
Author(s):  
Thaiphi Luu ◽  
Julie F. Cheung ◽  
Jennifer Baccon ◽  
Hanspeter Waldner
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Experimental Autoimmune Encephalomyelitis ◽  
T Cell Responses ◽  
Proteolipid Protein ◽  
Cell Receptor ◽  
Autoimmune Encephalomyelitis ◽  
Cell Responses ◽  
Experimental Autoimmune

Experimental autoimmune encephalomyelitis (EAE) is an established animal model of multiple sclerosis (MS). Inflammatory CD4+ T cell responses directed against CNS antigens, including myelin proteolipid protein (PLP), are key mediators of EAE. Dendritic cells (DCs) are critical for the induction of T cell responses against infectious agents. However, the importance of DCs in priming self-reactive CD4+ T cells in autoimmune disease such as MS has been unclear. To determine the requirement of DCs in PLP-specific CD4+ T cell responses and EAE, we genetically deleted CD11c+ DCs in PLP T cell receptor (TCR) transgenic SJL mice constitutively. DC deficiency did not impair the development, selection or the pathogenic function of PLP-specific CD4+ T cells in these mice, and resulted in accelerated spontaneous EAE compared to DC sufficient controls. In addition, using a genetic approach to ablate DCs conditionally in SJL mice, we show that CD11c+ DCs were dispensable for presenting exogenous or endogenous myelin antigen to PLP-specific T cells and for promoting pro-inflammatory T cell responses and severe EAE. Our findings demonstrate that constitutive or conditional ablation of CD11c+ DCs diminished self-tolerance to PLP autoantigen. They further show that in the absence of DCs, non-DCs can efficiently present CNS myelin antigens such as PLP to self-reactive T cells, resulting in accelerated onset of spontaneous or induced EAE.

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