Lipopolysaccharide injection induces relapses of experimental autoimmune encephalomyelitis in nontransgenic mice via bystander activation of autoreactive CD4+ cells.
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.
Deutsches Rheumaforschungszentrum Berlin, Berlin, Germany.
Axel
A
Nogai
Volker
V
Siffrin
Kerstin
K
Bonhagen
Caspar F
CF
Pfueller
Thordis
T
Hohnstein
Rudolf
R
Volkmer-Engert
Wolfgang
W
Brück
Christine
C
Stadelmann
Thomas
T
Kamradt
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D018122:B7-1 Antigen / Q000502:physiology; D051940:B7-2 Antigen; D024201:Bystander Effect / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D012008:Recurrence; D012486:Salmonella typhimurium / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016572:Cyclosporine