Odoardi, Francesca

[["dc.bibliographiccitation.firstpage","1805"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Journal of Experimental Medicine"],["dc.bibliographiccitation.lastpage","1814"],["dc.bibliographiccitation.volume","201"],["dc.contributor.author","Kawakami, Naoto"],["dc.contributor.author","Nägerl, U Valentin"],["dc.contributor.author","Odoardi, Francesca"],["dc.contributor.author","Bonhoeffer, Tobias"],["dc.contributor.author","Wekerle, Hartmut"],["dc.contributor.author","Flügel, Alexander"],["dc.date.accessioned","2020-07-06T13:58:17Z"],["dc.date.available","2020-07-06T13:58:17Z"],["dc.date.issued","2005-06-06"],["dc.description.abstract","We tracked pathogenic myelin basic protein-specific CD4+ effector T cells in early central nervous system (CNS) lesions of experimental autoimmune encephalomyelitis (EAE) by combining two-photon imaging and fluorescence video microscopy. We made two key observations: (a) the majority of the cells (65%) moved fast (maximal speed 25 microm/min) and apparently nondirected through the compact tissue; and (b) a second group of effector T cells (35%) appeared tethered to a fixed point. Polarization of T cell receptor and adhesion molecules (lymphocyte function-associated antigen 1) towards this fixed point suggests the formation of immune synapses. Nonpathogenic, ovalbumin-specific T cells were not tethered in the CNS and did not form synapse-like contacts, but moved through the tissue. After intrathecal injection of antigen, 40% of ovalbumin-specific T cells became tethered. Conversely, injection of anti-major histocompatibility complex class II antibodies profoundly reduced the number of stationary pathogenic T cells within the CNS (to 15%). We propose that rapid penetration of the CNS parenchyma by numerous autoimmune effector T cells along with multiple autoantigen-presentation events are responsible for the fulminate development of clinical EAE."],["dc.identifier.doi","10.1084/jem.20050011"],["dc.identifier.pmid","15939794"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66867"],["dc.language.iso","en"],["dc.relation.issn","0022-1007"],["dc.title","Live imaging of effector cell trafficking and autoantigen recognition within the unfolding autoimmune encephalomyelitis lesion"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","69"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","The Journal of Immunology"],["dc.bibliographiccitation.lastpage","81"],["dc.bibliographiccitation.volume","175"],["dc.contributor.author","Kawakami, Naoto"],["dc.contributor.author","Odoardi, Francesca"],["dc.contributor.author","Ziemssen, Tjalf"],["dc.contributor.author","Bradl, Monika"],["dc.contributor.author","Ritter, Thomas"],["dc.contributor.author","Neuhaus, Oliver"],["dc.contributor.author","Lassmann, Hans"],["dc.contributor.author","Wekerle, Hartmut"],["dc.contributor.author","Flügel, Alexander"],["dc.date.accessioned","2020-07-06T13:58:28Z"],["dc.date.available","2020-07-06T13:58:28Z"],["dc.date.issued","2005-07-01"],["dc.description.abstract","We embedded green fluorescent CD4(+) T cells specific for myelin basic protein (MBP) (T(MBP-GFP) cells) in the immune system of syngeneic neonatal rats. These cells persisted in the animals for the entire observation period spanning >2 years without affecting the health of the hosts. They maintained a memory phenotype with low levels of L-selectin and CD45RC, but high CD44. Although persisting in low numbers (0.01-0.1% of lymph node cells) they were sufficient to raise susceptibility toward clinical autoimmune disease. Immunization with MBP in IFA induced CNS inflammation and overt clinical disease in animals carrying neonatally transferred T(MBP-GFP) cells, but not in controls. The onset of the clinical disease coincided with mass infiltration of T(MBP-GFP) cells into the CNS. In the periphery, following the amplification phase a rapid contraction of the T cell population was observed. However, elevated numbers of fully reactive T(MBP-GFP) cells remained in the peripheral immune system after acute experimental autoimmune encephalomyelitis mediating reimmunization-induced disease relapses."],["dc.identifier.doi","10.4049/jimmunol.175.1.69"],["dc.identifier.pmid","15972633"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66869"],["dc.language.iso","en"],["dc.relation.issn","0022-1767"],["dc.title","Autoimmune CD4+ T cell memory: lifelong persistence of encephalitogenic T cell clones in healthy immune repertoires"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","86"],["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Journal of Neuroimmunology"],["dc.bibliographiccitation.lastpage","97"],["dc.bibliographiccitation.volume","191"],["dc.contributor.author","Flügel, Alexander"],["dc.contributor.author","Odoardi, Francesca"],["dc.contributor.author","Nosov, Mikhail"],["dc.contributor.author","Kawakami, Naoto"],["dc.date.accessioned","2020-07-06T13:57:58Z"],["dc.date.available","2020-07-06T13:57:58Z"],["dc.date.issued","2007-11"],["dc.description.abstract","Two photon microscopy (TPM) recently emerged as optical tool for the visualization of immune processes hundreds of micrometers deep in living tissue and organs. Here we summarize recent work on exploiting this technology to study brain antigen specific T cells. These cells are the cause of Experimental Autoimmune Encephalomyelitis (EAE) an autoimmune disease model of Multiple Sclerosis. TPM studies elucidated the dynamics of the autoaggressive effector T cells in peripheral immune milieus during preclinical EAE, where the cells become reprogrammed to enter their target organ. These studies revealed an unexpectedly lively locomotion behavior of the cells interrupted only by short-lasting contacts with the local immune stroma. Live T cell behavior was furthermore studied within the acutely inflamed CNS. Two distinct migratory patterns of the T cells were found: the majority of cells (60-70%) moved fast and seemingly unhindered through the compact CNS parenchyma. The motility of the other cell fraction was highly confined. The cells swung around a fixed cell pole forming long-lasting contacts to putative local antigen presenting cells."],["dc.identifier.doi","10.1016/j.jneuroim.2007.09.017"],["dc.identifier.pmid","17976745"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66864"],["dc.language.iso","en"],["dc.relation.issn","0165-5728"],["dc.title","Autoaggressive effector T cells in the course of experimental autoimmune encephalomyelitis visualized in the light of two-photon microscopy"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","920"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences of the United States of America"],["dc.bibliographiccitation.lastpage","925"],["dc.bibliographiccitation.volume","104"],["dc.contributor.author","Odoardi, Francesca"],["dc.contributor.author","Kawakami, Naoto"],["dc.contributor.author","Li, Zhaoxia"],["dc.contributor.author","Cordiglieri, Chiara"],["dc.contributor.author","Streyl, Kristina"],["dc.contributor.author","Nosov, Mikhail"],["dc.contributor.author","Klinkert, Wolfgang E F"],["dc.contributor.author","Ellwart, Joachim W"],["dc.contributor.author","Bauer, Jan"],["dc.contributor.author","Lassmann, Hans"],["dc.contributor.author","Wekerle, Hartmut"],["dc.contributor.author","Flügel, Alexander"],["dc.date.accessioned","2020-07-06T13:58:50Z"],["dc.date.available","2020-07-06T13:58:50Z"],["dc.date.issued","2007-01-16"],["dc.description.abstract","i.v. infusion of native autoantigen or its altered peptide variants is an important therapeutic option for the treatment of autoimmune diseases, because it selectively targets the disease-inducing T cells. To learn more about the mechanisms and kinetics of this approach, we visualized the crucial initial effects of i.v. infusion of peptides or intact protein on GFP-tagged autoaggressive CD4(+) effector T cells using live-video and two-photon in situ imaging of spleens in living animals. We found that the time interval between i.v. injection of intact protein to first changes in T cell behavior was extremely short; within 10 min after protein application, the motility of the T cells changed drastically. They slowed down and became tethered to local sessile stromal cells. A part of the cells aggregated to form clusters. Within the following 20 min, IFN-gamma mRNA was massively (>100-fold) up-regulated; surface IL-2 receptor and OX-40 (CD 134) increased 1.5 h later. These processes depleted autoimmune T cells in the blood circulation, trapping the cells in the peripheral lymphoid organs and thus preventing them from invading the CNS. This specific blockage almost completely abrogated CNS inflammation and clinical disease. These findings highlight the speed and efficiency of antigen recognition in vivo and add to our understanding of T cell-mediated autoimmunity."],["dc.identifier.doi","10.1073/pnas.0608383104"],["dc.identifier.pmid","17213317"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66870"],["dc.language.iso","en"],["dc.relation.issn","0027-8424"],["dc.title","Instant effect of soluble antigen on effector T cells in peripheral immune organs during immunotherapy of autoimmune encephalomyelitis"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","185"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Experimental Medicine"],["dc.bibliographiccitation.lastpage","197"],["dc.bibliographiccitation.volume","199"],["dc.contributor.author","Kawakami, Naoto"],["dc.contributor.author","Lassmann, Silke"],["dc.contributor.author","Li, Zhaoxia"],["dc.contributor.author","Odoardi, Francesca"],["dc.contributor.author","Ritter, Thomas"],["dc.contributor.author","Ziemssen, Tjalf"],["dc.contributor.author","Klinkert, Wolfgang E F"],["dc.contributor.author","Ellwart, Joachim W"],["dc.contributor.author","Bradl, Monika"],["dc.contributor.author","Krivacic, Kimberly"],["dc.contributor.author","Lassmann, Hans"],["dc.contributor.author","Ransohoff, Richard M"],["dc.contributor.author","Volk, Hans-Dieter"],["dc.contributor.author","Wekerle, Hartmut"],["dc.contributor.author","Linington, Christopher"],["dc.contributor.author","Flügel, Alexander"],["dc.date.accessioned","2020-07-06T13:58:55Z"],["dc.date.available","2020-07-06T13:58:55Z"],["dc.date.issued","2004-01-19"],["dc.description.abstract","The clinical picture of experimental autoimmune encephalomyelitis (EAE) is critically dependent on the nature of the target autoantigen and the genetic background of the experimental animals. Potentially lethal EAE is mediated by myelin basic protein (MBP)-specific T cells in Lewis rats, whereas transfer of S100beta- or myelin oligodendrocyte glycoprotein (MOG)-specific T cells causes intense inflammatory response in the central nervous system (CNS) with minimal disease. However, in Dark Agouti rats, the pathogenicity of MOG-specific T cells resembles the one of MBP-specific T cells in the Lewis rat. Using retrovirally transduced green fluorescent T cells, we now report that differential disease activity reflects different levels of autoreactive effector T cell activation in their target tissue. Irrespective of their pathogenicity, the migratory activity, gene expression patterns, and immigration of green fluorescent protein(+) T cells into the CNS were similar. However, exclusively highly pathogenic T cells were significantly reactivated within the CNS. Without local effector T cell activation, production of monocyte chemoattractants was insufficient to initiate and propagate a full inflammatory response. Low-level reactivation of weakly pathogenic T cells was not due to anergy because these cells could be activated by specific antigen in situ as well as after isolation ex vivo."],["dc.identifier.doi","10.1084/jem.20031064"],["dc.identifier.pmid","14734524"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66871"],["dc.language.iso","en"],["dc.relation.issn","0022-1007"],["dc.title","The activation status of neuroantigen-specific T cells in the target organ determines the clinical outcome of autoimmune encephalomyelitis"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]