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Lipopolysaccharide injection induces relapses of experimental autoimmune encephalomyelitis in nontransgenic mice via bystander activation of autoreactive CD4+ cells

Item Type:Article
Title:Lipopolysaccharide injection induces relapses of experimental autoimmune encephalomyelitis in nontransgenic mice via bystander activation of autoreactive CD4+ cells
Creators Name:Nogai, A. and Siffrin, V. and Bonhagen, K. and Pfueller, C.F. and Hohnstein, T. and Volkmer-Engert, R. and Brueck, W. and Stadelmann, C. and Kamradt, T.
Abstract:Infections sometimes associate with exacerbations of autoimmune diseases through pathways that are poorly understood. Ag-specific mechanisms such as cross-reactivity between a microbial Ag and a self-Ag have received no direct support. In this study, we show that injection of LPS induces experimental autoimmune encephalomyelitis in TCR-transgenic mice and relapse of encephalomyelitis in normal mice. This form of treatment induces proliferation and cytokine production in a fraction of effector/memory Th lymphocytes in vitro via physical contact of Th cells with CD4(-) LPS-responsive cells. TCR-mediated signals are not necessary; rather what is required is ligation of costimulatory receptors on Th cells by costimulatory molecules on the CD4(-) cells. This form of bystander activation provides an Ag-independent link between infection and autoimmunity that might fit the clinical and epidemiological data on the connection between infection and autoimmunity better than the Ag-specific models.
Keywords:Amino Acid Sequence, Bystander Effect, CD Antigens, CD4-Positive T-Lymphocytes, CD80 Antigens, CD86 Antigens, Cell Communication, Cultured Cells, Cyclosporine, Experimental Autoimmune Encephalomyelitis, Helper-Inducer T-Lymphocytes, Inbred C57BL Mice, Intravenous Injections, Knockout Mice, Lipopolysaccharides, Lymphocyte Activation, Membrane Glycoproteins, Molecular Sequence Data, Recurrence, Salmonella typhimurium, Transgenic Mice, Animals, Mice
Source:Journal of Immunology
ISSN:0022-1767
Publisher:American Association of Immunologists (U.S.A.)
Volume:175
Number:2
Page Range:959-966
Date:15 July 2005
Official Publication:https://doi.org/10.4049/jimmunol.175.2.959
PubMed:View item in PubMed

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