Fischer, Henrike J.

[["dc.bibliographiccitation.firstpage","17"],["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Journal of Neuroimmunology"],["dc.bibliographiccitation.lastpage","27"],["dc.bibliographiccitation.volume","260"],["dc.contributor.author","Camara, Monika"],["dc.contributor.author","Beyersdorf, Niklas"],["dc.contributor.author","Fischer, Henrike J."],["dc.contributor.author","Herold, Marco J."],["dc.contributor.author","Ip, Chi Wang"],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Toyka, Klaus V."],["dc.contributor.author","Taurog, Joel D."],["dc.contributor.author","Huenig, Thomas"],["dc.contributor.author","Herrmann, Thomas R."],["dc.contributor.author","Reichardt, Holger Michael"],["dc.contributor.author","Weishaupt, Andreas"],["dc.contributor.author","Kerkau, Thomas"],["dc.date.accessioned","2018-11-07T09:22:23Z"],["dc.date.available","2018-11-07T09:22:23Z"],["dc.date.issued","2013"],["dc.description.abstract","The role of CD8(+) T cells in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) is still unclear. We describe here significantly reduced disease activity of EAE both in Lewis rats, depleted of CD8(+) T cells by monoclonal antibodies and CD8 knockout rats, which was accompanied by reduced leukocyte infiltration into the spinal cord. We detected myelin basic protein (MBP)-specific CD4(+) T cells in peripheral lymphoid organs of CD8-depleted animals which, however, failed to differentiate into interferon-gamma-producing effector cells. Our results indicate that CD8(+) T cells interact with myelin-specific CD4(+) T cells early in EAE enabling them to differentiate into pathogenic effector cells. (C) 2013 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.jneuroim.2013.04.014"],["dc.identifier.isi","000321093000003"],["dc.identifier.pmid","23664330"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29330"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","0165-5728"],["dc.title","CD8(+) T cell help is required for efficient induction of EAE in Lewis rats"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","26"],["dc.bibliographiccitation.journal","Journal of Neuroimmunology"],["dc.bibliographiccitation.lastpage","32"],["dc.bibliographiccitation.volume","290"],["dc.contributor.author","Fischer, Henrike J."],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Lingner, Thomas"],["dc.contributor.author","Odoardi, Francesca"],["dc.contributor.author","Fluegel, Alexander"],["dc.contributor.author","Weishaupt, Andreas"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.date.accessioned","2018-11-07T10:19:23Z"],["dc.date.available","2018-11-07T10:19:23Z"],["dc.date.issued","2016"],["dc.description.abstract","MS is a highly prevalent neuroinflammatory disease of presumed autoimmune origin. Clinical observations and animal studies suggest that CD8(+) T cells play an important role in MS but their exact mechanisms are ill defined. When we actively induced EAE in CD8 knock-out DA rats, or adoptively transferred encephalitogenic CD4(+) T cells into CD8 knock-out DA rats, the disease course was indistinguishable from controls. Since our previous findings had revealed that the absence of CD8(+) T cells in Lewis rats ameliorated EAE, we compared antigen-induced T cell differentiation in both strains. Disease onset and the composition of the draining lymph nodes were similar but T cell activation in DA rats was much weaker. Moreover, oligoclonal expansion of CD8(+) T cells was exclusively observed in Lewis but not in DA rats. This suggests that myelin-specific CD8(+) T cells are involved in the differentiation of encephalitogenic CD4(+) T cells in Lewis rats, whilst they do not impact CD4(+) T cell priming in DA rats. Hence, clonal expansion of CD8(+) T cells in secondary lymphoid organs appears to be linked to their ability to modulate CNS autoimmune responses. (C) 2015 Published by Elsevier B.V."],["dc.description.sponsorship","German Research Foundation (DFG) [SFB/TRR 43]"],["dc.identifier.doi","10.1016/j.jneuroim.2015.10.020"],["dc.identifier.isi","000368955000005"],["dc.identifier.pmid","26711565"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41645"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","1872-8421"],["dc.relation.issn","0165-5728"],["dc.title","Modulation of CNS autoimmune responses by CD8(+) T cells coincides with their oligoclonal expansion"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Journal of Neuroimmunology"],["dc.bibliographiccitation.volume","253"],["dc.contributor.author","Fischer, Henrike J."],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.date.accessioned","2018-11-07T09:02:15Z"],["dc.date.available","2018-11-07T09:02:15Z"],["dc.date.issued","2012"],["dc.format.extent","46"],["dc.identifier.isi","000312764800124"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24639"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.publisher.place","Amsterdam"],["dc.relation.conference","11th International Congress of Neuroimmunology (ISNI)"],["dc.relation.eventlocation","Boston, MA"],["dc.relation.issn","0165-5728"],["dc.title","Gimap5 deficiency in Lewis rats causes lymphopenia and exacerbates Experimental Autoimmune Encephalomyelitis"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","713"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","729"],["dc.bibliographiccitation.volume","127"],["dc.contributor.author","Schweingruber, Nils"],["dc.contributor.author","Fischer, Henrike J."],["dc.contributor.author","Fischer, Lisa"],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Karabinskaya, Anna"],["dc.contributor.author","Labi, Verena"],["dc.contributor.author","Villunger, Andreas"],["dc.contributor.author","Kretzschmar, Benedikt"],["dc.contributor.author","Huppke, Peter"],["dc.contributor.author","Simons, Mikael"],["dc.contributor.author","Tuckermann, Jan P."],["dc.contributor.author","Fluegel, Alexander"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.date.accessioned","2018-11-07T09:40:54Z"],["dc.date.available","2018-11-07T09:40:54Z"],["dc.date.issued","2014"],["dc.description.abstract","Glucocorticoids (GCs) are the standard therapy for treating multiple sclerosis (MS) patients suffering from an acute relapse. One of the main mechanisms of GC action is held to be the induction of T cell apoptosis leading to reduced lymphocyte infiltration into the CNS, yet our analysis of experimental autoimmune encephalomyelitis (EAE) in three different strains of genetically manipulated mice has revealed that the induction of T cell apoptosis is not essential for the therapeutic efficacy of GCs. Instead, we identified the redirection of T cell migration in response to chemokines as a new therapeutic principle of GC action. GCs inhibited the migration of T cells towards CCL19 while they enhanced their responsiveness towards CXCL12. Importantly, blocking CXCR4 signaling in vivo by applying Plerixafor(A (R)) strongly impaired the capacity of GCs to interfere with EAE, as revealed by an aggravated disease course, more pronounced CNS infiltration and a more dispersed distribution of the infiltrating T cells throughout the parenchyma. Our observation that T cells lacking the GC receptor were refractory to CXCL12 further underscores the importance of this pathway for the treatment of EAE by GCs. Importantly, methylprednisolone pulse therapy strongly increased the capacity of peripheral blood T cells from MS patients of different subtypes to migrate towards CXCL12. This indicates that modulation of T cell migration is an important mechanistic principle responsible for the efficacy of high-dose GC therapy not only of EAE but also of MS."],["dc.identifier.doi","10.1007/s00401-014-1248-4"],["dc.identifier.isi","000334426300007"],["dc.identifier.pmid","24488308"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33606"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","1432-0533"],["dc.relation.issn","0001-6322"],["dc.title","Chemokine-mediated redirection of T cells constitutes a critical mechanism of glucocorticoid therapy in autoimmune CNS responses"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4360"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","The Journal of Immunology"],["dc.bibliographiccitation.lastpage","4370"],["dc.bibliographiccitation.volume","190"],["dc.contributor.author","Mueller, Nora"],["dc.contributor.author","Fischer, Henrike J."],["dc.contributor.author","Tischner, Denise"],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.date.accessioned","2018-11-07T09:25:59Z"],["dc.date.available","2018-11-07T09:25:59Z"],["dc.date.issued","2013"],["dc.description.abstract","Glucocorticoids (GCs) repress lymphocyte function by controlling gene expression. In this study, we investigated Ag-specific effector T cells and provide evidence that GCs also modulate these cells' cytoskeletal architecture by nongenomic mechanisms. Following GC treatment, effector T cells rapidly lose their polarized morphology, which impedes both their migratory capacity and their interaction with APCs. The cytoskeleton rearrangements are preceded by an activation of ezrin-radixin-moesin proteins, which transiently increases the cellular rigidity but seems to occur independently of altered tyrosine phosphorylation. Phospholipase C activity is critically involved in mediating these nongenomic effects, because its inhibition prevents both T cell depolarization and ezrin-radixin-moesin phosphorylation after GC exposure. GC administration in vivo induced similar morphological changes in effector T cells as observed in vitro, suggesting that the above process plays a role in modulating inflammatory diseases. Taken together, our findings identify a novel mechanism through which GCs rapidly repress T cell function independently of gene transcription. The Journal of Immunology, 2013, 190: 4360-4370."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [LU 634/8-1, RE 1631/10-1, SFB/TRR 43]"],["dc.identifier.doi","10.4049/jimmunol.1201520"],["dc.identifier.isi","000317274500053"],["dc.identifier.pmid","23475220"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30195"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Immunologists"],["dc.relation.issn","0022-1767"],["dc.title","Glucocorticoids Induce Effector T Cell Depolarization via ERM Proteins, Thereby Impeding Migration and APC Conjugation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1724"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","The FASEB Journal"],["dc.bibliographiccitation.lastpage","1732"],["dc.bibliographiccitation.volume","30"],["dc.contributor.author","Fischer, Henrike J."],["dc.contributor.author","Witte, Ann-Kathrin"],["dc.contributor.author","Walter, Lutz"],["dc.contributor.author","Groene, Hermann-Josef"],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.date.accessioned","2018-11-07T10:15:09Z"],["dc.date.available","2018-11-07T10:15:09Z"],["dc.date.issued","2016"],["dc.description.abstract","T-cell lymphopenia is a major risk factor for autoimmunity. Here we describe congenic Lewis (LEW) rats with a loss-of-function mutation in the Gimap5 gene, leading to a 92% reduction in peripheral T-cell numbers. Gimap5-deficient LEW rats developed eosinophilic autoimmune gastroenteritis accompanied by a 40-fold increase in IgE serum levels. This phenotype was ameliorated by antibiotic treatment, indicating a critical role of the microbial flora in the development of inflammatory bowel disease. Interestingly, Gimap5-deficient LEW rats showed strongly aggravated experimental autoimmune encephalomyelitis (EAE) after immunization with guinea pig myelin basic protein. This phenotype, however, persisted after antibiosis, confirming that the enhanced CNS autoimmune response in T-cell lymphopenic Gimap5-deficient LEW rats was unrelated to the composition of the microbial flora. Rather, it seems that it was caused by the 7-fold increase in the percentage of activated T cells producing IL-17 and IFN-gamma, and the skewed T-cell receptor (TCR) repertoire, both of which were the result of T-cell lymphopenia and not affected by antibiosis. This notion was supported by the observation that adoptive T-cell transfer corrected the TCR repertoire and improved EAE. Collectively, our findings confirm a critical albeit differential role of T-cell lymphopenia in the susceptibility to organ-specific autoimmune responses.-Fischer, H.J., Witte, A.-K., Walter, L., Grone, H.-J., van den Brandt, J., Reichardt, H.M. Distinct roles of T-cell lymphopenia and the microbial flora for gastrointestinal and CNS autoimmunity."],["dc.identifier.doi","10.1096/fj.15-277384"],["dc.identifier.isi","000374879400004"],["dc.identifier.pmid","26740263"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40753"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Federation Amer Soc Exp Biol"],["dc.relation.issn","1530-6860"],["dc.relation.issn","0892-6638"],["dc.title","Distinct roles of T-cell lymphopenia and the microbial flora for gastrointestinal and CNS autoimmunity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2285"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","The Journal of Immunology"],["dc.bibliographiccitation.lastpage","2294"],["dc.bibliographiccitation.volume","185"],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Fischer, Henrike J."],["dc.contributor.author","Walter, Lutz"],["dc.contributor.author","Huenig, Thomas"],["dc.contributor.author","Kloeting, Ingrid"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.date.accessioned","2018-11-07T08:40:21Z"],["dc.date.available","2018-11-07T08:40:21Z"],["dc.date.issued","2010"],["dc.description.abstract","Diabetes-prone BioBreeding (DP-BB) rats spontaneously develop type 1 diabetes mellitus (T1DM) on grounds of their MHC haplotype RT1(u) and a point mutation in the Gimap5 gene. In this study, we report that DP-BB rats exhibit an increasingly severe imbalance, in particular between Th17 and regulatory T (T(reg)) cells, within the first months of age. This can be assigned to an excess in effector T cells because neither the percentage nor the function of the T(reg) cells is compromised. Flow cytometric analysis of V beta segment usage and CDR3 spectratyping further suggest that the disturbed repertoire of peripheral T cells may also contribute to the development of T1DM in DP-BB rats. Importantly, expansion of T(reg) cells in vivo by means of a CD28 super-agonistic Ab as well as adoptive transfer of T(reg) cells efficiently interferes with the development of T1DM in DP-BB rats, whereas treatment with conventional Th cells does not afford protection. Using a newly generated strain of enhanced GFP transgenic rats, we could further demonstrate that the transferred T(reg) cells persist in the recipient rats for several months and partially correct the imbalance between Th17 and T(reg) cells. Thus, our data support the hypothesis that unchecked effector T cell action and a disturbed T cell repertoire contribute to the development of T1DM in DP-BB rats, which may also have implications for a better understanding of the human disease. The Journal of Immunology, 2010, 185: 2285-2294."],["dc.description.sponsorship","Volkswagen Stiftung [I/75 403]"],["dc.identifier.doi","10.4049/jimmunol.1000462"],["dc.identifier.isi","000280661900036"],["dc.identifier.pmid","20644174"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19214"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Immunologists"],["dc.relation.issn","0022-1767"],["dc.title","Type 1 Diabetes in BioBreeding Rats Is Critically Linked to an Imbalance between Th17 and Regulatory T Cells and an Altered TCR Repertoire"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Immunology"],["dc.bibliographiccitation.volume","137"],["dc.contributor.author","Fischer, Henrike J."],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.date.accessioned","2018-11-07T09:06:25Z"],["dc.date.available","2018-11-07T09:06:25Z"],["dc.date.issued","2012"],["dc.format.extent","481"],["dc.identifier.isi","000309189104048"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25552"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.publisher.place","Hoboken"],["dc.relation.conference","European Congress of Immunology"],["dc.relation.eventlocation","Glasgow, SCOTLAND"],["dc.relation.issn","0019-2805"],["dc.title","Mutant Gimap5 derived from diabetes-prone BB rats causes selective enrichment of Th1/Th17 cells and an altered TCR repertoire in Lewis rats"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1910"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","The Journal of Immunology"],["dc.bibliographiccitation.lastpage","1920"],["dc.bibliographiccitation.volume","198"],["dc.contributor.author","Fischer, Henrike J."],["dc.contributor.author","Sie, Christopher"],["dc.contributor.author","Schumann, Eric"],["dc.contributor.author","Witte, Ann-Kathrin"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.date.accessioned","2018-11-07T10:27:04Z"],["dc.date.available","2018-11-07T10:27:04Z"],["dc.date.issued","2017"],["dc.description.abstract","T cell activation is an energy-demanding process fueled by increased glucose consumption and accompanied by upregulation of the insulin receptor (INSR). In this article, we report that silencing the INSR in inducible knockdown rats impairs selective T cell functions but not thymocyte development. Glucose transport and glycolysis in activated CD4(+) T cells were compromised in the absence of the INSR, which was associated with alterations in intracellular signaling pathways. The observed metabolic defects coincided with reduced cytokine production, proliferation, and migration, as well as increased apoptosis of CD4(+) T cells. The cytotoxicity of CD8(+) T cells in response to alloantigens was also diminished under these conditions, whereas the frequency and suppressive capacity of regulatory T cells were unaffected. The observed impairments proved to be decisive in vivo because silencing of the INSR attenuated clinical symptoms in animal models of acute graft-versus-host disease and multiple sclerosis. Taken together, our results suggest that upregulation of the INSR on T cells following activation is required for efficient adaptive immunity."],["dc.identifier.doi","10.4049/jimmunol.1601011"],["dc.identifier.isi","000395904000017"],["dc.identifier.pmid","28115529"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43175"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Amer Assoc Immunologists"],["dc.relation.issn","1550-6606"],["dc.relation.issn","0022-1767"],["dc.title","The Insulin Receptor Plays a Critical Role in T Cell Function and Adaptive Immunity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]