scholarly journals Intravenous Liposomal Prednisolone Downregulates In Situ TNF-α Production by T-cells in Experimental Autoimmune Encephalomyelitis

2003 ◽  
Vol 51 (9) ◽  
pp. 1241-1244 ◽  
Author(s):  
Jens Schmidt ◽  
Josbert M. Metselaar ◽  
Ralf Gold
Keyword(s):  
T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
High Dose ◽  
Autoimmune Encephalomyelitis ◽  
Double Labeling ◽  
Formalin Fixed Paraffin ◽  
Tnf Α ◽  
Formalin Fixed Paraffin Embedded ◽  
Factor Α ◽  
Experimental Autoimmune

Multiple sclerosis (MS) relapses are treated with high-dose IV glucocorticosteroids. Here we investigated mechanisms of long-circulating polyethylene glycol-coated liposomes encapsulating prednisolone (PL) in adoptive transfer experimental autoimmune encephalomyelitis. Rats received IV 10 mg/kg PL 6, 18, or 42 hr before sacrifice at disease maximum. In formalin-fixed, paraffin-embedded spinal cord we employed a nonfluorescent immunohistochemical (IHC) double labeling. We stained for tumor necrosis factor-α (TNF-α) in combination with a T-cell antigen. Compared with PBS-containing liposomes, PL at 18 hr, and more at 42 hr, significantly reduced the rate of TNF-α double-labeled T-cells. This correlated with an ameliorated disease score at day 5 after PL 42 hr. Our results help to further understand mechanisms of action of drug targeting by liposomal steroids, with possible implications for treatment of autoimmune disorders such as MS.

scholarly journals Tumor Necrosis Factor α and Lymphotoxin α Are Not Required for Induction of Acute Experimental Autoimmune Encephalomyelitis

1997 ◽  
Vol 185 (12) ◽  
pp. 2177-2182 ◽  
Author(s):  
Karl Frei ◽  
Hans-Pietro Eugster ◽  
Martin Bopst ◽  
Cris S. Constantinescu ◽  
Ehud Lavi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
T Cells ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Autoimmune Encephalomyelitis ◽  
Tnf Α ◽  
Factor Α ◽  
Lymphotoxin Α ◽  
Necrosis Factor ◽  
Experimental Autoimmune

Immunization of mice with myelin components results in experimental autoimmune encephalomyelitis (EAE), which is mediated by myelin-specific CD4+ T cells and anti-myelin antibodies. Tumor necrosis factor α (TNF-α) and lymphotoxin α (LT-α) are thought to be involved in the events leading to inflammatory demyelination in the central nervous system. To ascertain this hypothesis 129 × C57BL/6 mice with an inactivation of the tnf and lta genes (129 × C57BL/6−/−) and SJL/J mice derived from backcrosses of the above mentioned mutant mice (SJL−/−) were immunized with mouse spinal cord homogenate (MSCH) or proteolipid protein. Both 129 × C57BL/6−/− mice and SJL−/− mice developed EAE. In SJL−/− mice immunized with MSCH, a very severe form of EAE with weight loss, paralysis of all four limbs, and lethal outcome was observed. The histologic hallmark was an intense perivascular and parenchymal infiltration with predominantly CD4+ T cells and some CD8+ T cells associated with demyelination in both brain and spinal cord. These results indicate that TNF-α and LT-α are not essential for the development of EAE.

scholarly journals Selective targeting of regulatory T cells with CD28 superagonists allows effective therapy of experimental autoimmune encephalomyelitis

2005 ◽  
Vol 202 (3) ◽  
pp. 445-455 ◽  
Author(s):  
Niklas Beyersdorf ◽  
Stefanie Gaupp ◽  
Karen Balbach ◽  
Jens Schmidt ◽  
Klaus V. Toyka ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Cell Subset ◽  
High Dose ◽  
Autoimmune Encephalomyelitis ◽  
Lewis Rats ◽  
Experimental Autoimmune

CD4+CD25+ regulatory T cells (T reg cells) play a key role in controlling autoimmunity and inflammation. Therefore, therapeutic agents that are capable of elevating numbers or increasing effector functions of this T cell subset are highly desirable. In a previous report we showed that a superagonistic monoclonal antibody specific for rat CD28 (JJ316) expands and activates T reg cells in vivo and upon short-term in vitro culture. Here we demonstrate that application of very low dosages of the CD28 superagonist into normal Lewis rats is sufficient to induce T reg cell expansion in vivo without the generalized lymphocytosis observed with high dosages of JJ316. Single i.v. administration of a low dose of the CD28 superagonist into Dark Agouti (DA) rats or Lewis rats that suffered from experimental autoimmune encephalomyelitis (EAE) proved to be highly and equally efficacious as high-dose treatment. Finally, we show that T reg cells that were isolated from CD28-treated animals displayed enhanced suppressive activity toward myelin basic protein–specific T cells in vitro, and, upon adoptive transfer, protected recipients from EAE. Our data indicate that this class of CD28-specific monoclonal antibodies targets CD4+CD25+ T reg cells and provides a novel means for the effective treatment of multiple sclerosis and other autoimmune diseases.

scholarly journals Chloroquine Treatment Enhances Regulatory T Cells and Reduces the Severity of Experimental Autoimmune Encephalomyelitis

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e65913 ◽  
Author(s):  
Rodolfo Thomé ◽  
Adriel S. Moraes ◽  
André Luis Bombeiro ◽  
Alessandro dos Santos Farias ◽  
Carolina Francelin ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Autoimmune Encephalomyelitis ◽  
Chloroquine Treatment ◽  
Experimental Autoimmune

scholarly journals Mgat5 Deficiency in T Cells and Experimental Autoimmune Encephalomyelitis

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Ani Grigorian ◽  
Michael Demetriou
Keyword(s):  
T Cells ◽  
T Cell ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Demyelinating Disease ◽  
Cell Receptor ◽  
Protein Glycosylation ◽  
Autoimmune Encephalomyelitis ◽  
Glycosylation Pathway ◽  
Experimental Autoimmune ◽  
Surface Glycoproteins

Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease initiated by autoreactive T cells. Mgat5, a gene in the Asn (N-) linked protein glycosylation pathway, associates with MS severity and negatively regulates experimental autoimmune encephalomyelitis (EAE) and spontaneous inflammatory demyelination in mice. N-glycan branching by Mgat5 regulates interaction of surface glycoproteins with galectins, forming a molecular lattice that differentially controls the concentration of surface glycoproteins. T-cell receptor signaling, T-cell proliferation, TH1 differentiation, and CTLA-4 endocytosis are inhibited by Mgat5 branching. Non-T cells also contribute to MS pathogenesis and express abundant Mgat5 branched N-glycans. Here we explore whether Mgat5 deficiency in myelin-reactive T cells is sufficient to promote demyelinating disease. Adoptive transfer of myelin-reactive Mgat5−/− T cells into Mgat5+/+ versus Mgat5−/− recipients revealed more severe EAE in the latter, suggesting that Mgat5 branching deficiency in recipient naive T cells and/or non-T cells contribute to disease pathogenesis.

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