title: What causes relapses of autoimmune diseases? The etiological role of autoreactive T cells.
abstract: Most human autoimmune diseases have a relapsing-remitting or a chronic progressive course, while animal models are usually acute and monophasic. In our experimental animal model the disease can be either monophasic or remitting, depending on the autoantigen used for induction, and it appears to lie in the effector phenotype of the elicited T helper cell response. Since both, monophasic and relapsing courses of disease are induced by immunization as well as by adoptive transfer of peptide-specific, CD4(+) T cells, we were able to directly compare the transcriptomes of pathogenic T cell lines by gene array analysis and qPCR as well as protein expression. Upregulated genes were only determined in T cells inducing relapsing uveitis and belong to certain pathways of antigen presentation, activation, inflammation, migration and survival, comprising WNT, Hedgehog, MAP-kinase and JAK/STAT-pathways. These pathways are partially interacting with each other, and the central molecule upregulated in T cells causing relapsing disease was found to be IFN-γ. Here the course of the autoimmune diseases strictly depends on the characteristics of the autoreactive T cells, which are already determined at their early stage of antigen-specific activation. Our rat models of experimental autoimmune uveitis could help elucidating the immune mechanisms behind relapsing autoimmunity in order to develop better therapeutic strategies.
authors.affiliation: Klinikum der Universität München, Dept. of Ophthalmology, Mathildenstr. 8, 80336 Munich, Germany. Gerhild.Wildner@med.uni-muenchen.de
authors.forename: Gerhild
authors.initials: G
authors.lastname: Wildner
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kaufmann
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001324:Autoantigens / Q000009:adverse effects / Q000276:immunology; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000473:pathology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D051381:Rats; D011917:Rats, Inbred Lew; D012008:Recurrence; D014605:Uveitis / Q000209:etiology / Q000276:immunology / Q000473:pathology
chemical_list: D001324:Autoantigens; C000717609:Tgm2 protein, rat; D000091345:Protein Glutamine gamma Glutamyltransferase 2
keywords: Actg2; Casp; Cnksr1/Magi1; Ctsc; Ctsh; Cytokines; E-cadherin; EAU; ERK; Ecad; Gli1; Gzmg; HH; Hedgehog; Hla-dmb; IFN-gamma; IP-10/CXCL10; IRBP; JAK/STAT; JNK2/MAPK9; Jag1; Jak2; Janus kinase 2; Janus kinase/signal transducer and activator of transcription; LEF1; MAGUK; MAPK; MHC class II DM beta; MIF; NAD(P)H:quinone oxidoreductase 1; NFκB; NQO1; PCP; RT1 class II locus DA; Rab27a; Ralgps2; Ras-related protein 27A; Ras-specific guanine nucleotide-releasing factor 2; Rat model; Rt1.Da; Shh; Signaling transduction pathways; T cell factor 1; TCF-1; Tgm2; Uveitis; actin gamma 2; c-Jun N-terminal protein kinase/mitogen-activated protein kinase 9; caspase; cathepsin C; cathepsin H; connector enhancer of kinase suppressor of Ras 3/membrane-associated guanylate kinase-interacting protein-like 1; experimental autoimmune uveitis; extracellular signal-regulated kinase; glioma-associated oncogene homolog 1; granzyme G; interferon gamma-induced protein 10/interferon-inducible cytokine 10; interphotoreceptor retinoid-binding protein; jagged 1; lymphoid enhancer-binding factor 1; macrophage migration inhibitory factor; membrane-associated guanylate kinase; mitogen-activated protein kinase; nuclear factor kappa-light-chain-enhancer of activated B cells; planar cell polarity; qPCR; quantitative real time polymerase chain reaction; sonic hedgehog; transglutaminase 2