Pathogenesis of acute passive murine encephalomyelitis II. Th1 phenotype of the inducing population is not sufficient to cause disease.
The present study was designed to assess the pattern of cytokine expression over the course of disease in the central nervous system (CNS) of recipients of an encephalitogenic T-cell clone specific for proteolipid protein (PLP) peptide 139-151. Reverse transcriptase-polymerase chain reaction (RT-PCR) analyses of CNS mRNA from samples taken during the onset of acute disease demonstrated upregulation of message for cytokines involved in the recruitment and activation of macrophages (GM-CSF, interleukin (IL)-3, IL-9) and the inflammatory cytokines tumor necrosis factor (TNF)-alpha and iNOS as well as message for IL-10 and transforming growth factor (TGF)beta. During the recovery stage message for most cytokines was absent, but during relapse inflammatory cytokine messages were again detectable. Message for the accessory molecules B7-2 and CTLA-4 was observed only on the day of onset of acute experimental allergic encephalomyelitis (EAE) and at relapse. The messages for these molecules were downregulated at the onset of recovery. These results illustrate the dynamic nature of the immune response during the course of EAE, and support a model of disease in which T-cells are involved in the regulation of disease while a nonspecific inflammatory reaction is responsible for the CNS damage observed during EAE.
Lyons
J A
JA
Department of Microbiology, Medical College of Wisconsin, Milwaukee 53226, USA. lyonsj@neuro.wustl.edu
Zhao
M L
ML
Fritz
R B
RB
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology; D060908:CTLA-4 Antigen; D002999:Clone Cells; D017931:DNA Primers; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000276:immunology*; D000939:Epitopes; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology; D018796:Immunoconjugates; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D007377:Interleukin-3 / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D016906:Interleukin-9 / Q000235:genetics / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000201:enzymology / Q000276:immunology*; D018418:Th2 Cells / Q000201:enzymology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C497965:Cd86 protein, mouse; C556707:Ctla4 protein, mouse; D017931:DNA Primers; D000939:Epitopes; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D007377:Interleukin-3; D015850:Interleukin-6; D016906:Interleukin-9; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D000069594:Abatacept; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse