Lühder, Fred

[["dc.bibliographiccitation.artnumber","e4643"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Gogishvili, Tea"],["dc.contributor.author","Langenhorst, Daniela"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Elias, Fernando"],["dc.contributor.author","Elflein, Karin"],["dc.contributor.author","Dennehy, Kevin M."],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Huenig, Thomas"],["dc.date.accessioned","2018-11-07T08:32:35Z"],["dc.date.available","2018-11-07T08:32:35Z"],["dc.date.issued","2009"],["dc.description.abstract","Superagonistic CD28-specific monoclonal antibodies (CD28SA) are highly effective activators of regulatory T-cells (Treg cells) in rats, but a first-in-man trial of the human CD28SA TGN1412 resulted in an unexpected cytokine release syndrome. Using a novel mouse anti-mouse CD28SA, we re-investigate the relationship between Treg activation and systemic cytokine release. Treg activation by CD28SA was highly efficient but depended on paracrine IL-2 from CD28SA-stimulated conventional T-cells. Systemic cytokine levels were innocuous, but depletion of Treg cells prior to CD28SA stimulation led to systemic release of proinflammatory cytokines, indicating that in rodents, Treg cells effectively suppress the inflammatory response. Since the human volunteers of the TGN1412 study were not protected by this mechanism, we also tested whether corticosteroid prophylaxis would be compatible with CD28SA induced Treg activation. We show that neither the expansion nor the functional activation of Treg cells is affected by high-dose dexamethasone sufficient to control systemic cytokine release. Our findings warn that preclinical testing of activating biologicals in rodents may miss cytokine release syndromes due to the rapid and efficacious response of the rodent Treg compartment, and suggest that polyclonal Treg activation is feasible in the presence of antiphlogistic corticosteroid prophylaxis."],["dc.identifier.doi","10.1371/journal.pone.0004643"],["dc.identifier.isi","000265487800023"],["dc.identifier.pmid","19247496"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/5818"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17376"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Rapid Regulatory T-Cell Response Prevents Cytokine Storm in CD28 Superagonist Treated Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1644"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","European Journal of Immunology"],["dc.bibliographiccitation.lastpage","1655"],["dc.bibliographiccitation.volume","46"],["dc.contributor.author","Froehlich, Monika"],["dc.contributor.author","Gogishvili, Tea"],["dc.contributor.author","Langenhorst, Daniela"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Huenig, Thomas"],["dc.date.accessioned","2018-11-07T10:11:59Z"],["dc.date.available","2018-11-07T10:11:59Z"],["dc.date.issued","2016"],["dc.description.abstract","The role of CD28-mediated costimulation in secondary CD8(+) T-cell responses remains controversial. Here, we have used two tools - blocking mouse anti-mouse CD28-specific antibodies and inducible CD28-deleting mice - to obtain definitive answers in mice infected with ovalbumin-secreting Listeria monocytogenes. We report that both blockade and global deletion of CD28 reveal its requirement for full clonal expansion and effector functions such as degranulation and IFN-gamma production during the secondary immune response. In contrast, cell-intrinsic deletion of CD28 in transferred TCR-transgenic CD8(+) T cells before primary infection leads to impaired clonal expansion but an increase in cells able to express effector functions in both primary and secondary responses. We suggest that the proliferation-impaired CD8(+) T cells respond to CD28-dependent help from their environment by enhanced functional differentiation. Finally, we report that cell-intrinsic deletion of CD28 after the peak of the primary response does not affect the establishment, maintenance, or recall of long-term memory. Thus, if given sufficient time, the progeny of primed CD8(+) T cells adapt to the absence of this costimulator."],["dc.identifier.doi","10.1002/eji.201546232"],["dc.identifier.isi","000380752600013"],["dc.identifier.pmid","27122236"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40149"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1521-4141"],["dc.relation.issn","0014-2980"],["dc.title","Interrupting CD28 costimulation before antigen rechallenge affects CD8(+) T-cell expansion and effector functions during secondary response in mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1394"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Journal of Allergy and Clinical Immunology"],["dc.bibliographiccitation.lastpage","+"],["dc.bibliographiccitation.volume","130"],["dc.contributor.author","Gogishvili, Tea"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Kirstein, Frank"],["dc.contributor.author","Nieuwenhuizen, Natalie E."],["dc.contributor.author","Goebbels, Sandra"],["dc.contributor.author","Beer-Hammer, Sandra"],["dc.contributor.author","Pfeffer, Klaus"],["dc.contributor.author","Reuter, Sebastian"],["dc.contributor.author","Taube, Christian"],["dc.contributor.author","Brombacher, Frank"],["dc.contributor.author","Huenig, Thomas"],["dc.date.accessioned","2018-11-07T09:02:49Z"],["dc.date.available","2018-11-07T09:02:49Z"],["dc.date.issued","2012"],["dc.description.abstract","Background: Allergic asthma is a T(H)2-promoted hyperreactivity with an immediate, IgE, and mast cell-dependent response followed by eosinophil-dominated inflammation and airway obstruction. Objective: Because costimulation by CD28 is essential for T(H)2 but not T(H)1 responses, we investigated the effect of selective interference with this pathway in mice using the models of ovalbumin and house dust mite-induced airway inflammation. Methods: To study the role of CD28 in the effector phase of allergic airway inflammation, we developed an inducibly CD28-deleting mouse strain or alternatively used a CD28 ligand-binding site-specific mouse anti-mouse mAb blocking CD28 engagement. Results: We show that even after systemic sensitization to the allergen, interruption of CD28-mediated costimulation is highly effective in preventing airway inflammation during challenge. In addition to improving airway resistance and histopathologic presentation and reducing inflammatory infiltrates, antibody treatment during allergen challenge resulted in a marked relative increase in regulatory T-cell numbers among the CD4 T-cell subset of the challenged lung. Conclusion: Selective interference with CD28-mediated costimulation during allergen exposure might be an attractive therapeutic concept for allergic asthma. (J Allergy Clin Immunol 2012;130:1394-403.)"],["dc.identifier.doi","10.1016/j.jaci.2012.08.049"],["dc.identifier.isi","000311641100021"],["dc.identifier.pmid","23102920"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24769"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Mosby-elsevier"],["dc.relation.issn","0091-6749"],["dc.title","Interruption of CD28-mediated costimulation during allergen challenge protects mice from allergic airway disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Annals of the Rheumatic Diseases"],["dc.bibliographiccitation.volume","65"],["dc.contributor.author","Huenig, Thomas"],["dc.contributor.author","Beyersdorf, Niklas"],["dc.contributor.author","Dennehy, Kevin M."],["dc.contributor.author","Lin, C."],["dc.contributor.author","Ellas, F."],["dc.contributor.author","Kerkau, Thomas"],["dc.contributor.author","Gaupp, S."],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Na, S."],["dc.contributor.author","Gold, Ralf"],["dc.date.accessioned","2018-11-07T09:33:24Z"],["dc.date.available","2018-11-07T09:33:24Z"],["dc.date.issued","2006"],["dc.format.extent","27"],["dc.identifier.isi","000249372500079"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31958"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","B M J Publishing Group"],["dc.publisher.place","London"],["dc.relation.conference","Annual European Congress of Rheumatology (EULAR 2006)"],["dc.relation.eventlocation","Amsterdam, NETHERLANDS"],["dc.relation.issn","0003-4967"],["dc.title","CD28-stimulated expansion of regulatory T-cells"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","239"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Medical Microbiology and Immunology"],["dc.bibliographiccitation.lastpage","246"],["dc.bibliographiccitation.volume","199"],["dc.contributor.author","Huenig, Thomas"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Elflein, Karin"],["dc.contributor.author","Gogishvili, Tea"],["dc.contributor.author","Froehlich, Monika"],["dc.contributor.author","Guler, Reto"],["dc.contributor.author","Cutler, Antony"],["dc.contributor.author","Brombacher, Frank"],["dc.date.accessioned","2018-11-07T08:40:58Z"],["dc.date.available","2018-11-07T08:40:58Z"],["dc.date.issued","2010"],["dc.description.abstract","The costimulatory receptor CD28 and IL-4R alpha-containing cytokine receptors play key roles in controlling the size and quality of pathogen-specific immune responses. Thus, CD28-mediated costimulation is needed for effective primary T-cell expansion and for the generation and activation of regulatory T-cells (Treg cells), which protect from immunopathology. Similarly, IL-4R alpha signals are required for alternative activation of macrophages, which counteract inflammation by type 1 responses. Furthermore, immune modulation by CD28 and IL-4 is interconnected through the promotion of IL-4 producing T-helper 2 cells by CD28 signals. Using conditionally IL-4R alpha and CD28 deleting mice, as well as monoclonal antibodies, which block or stimulate CD28, or mAb that deplete Treg cells, we have studied the roles of CD28 and IL-4R alpha in experimental mouse models of virus (influenza), intracellular bacteria (L. monocytogenes, M. tuberculosis), and parasite infections (T. congolense, L. major). We observed that in some, but not all settings, Treg cells and type 2 immune deviation, including activation of alternative macrophages can be manipulated to protect the host either from infection or from immunopathology with an overall beneficial outcome. Furthermore, we provide direct evidence that secondary CD8 T-cell responses to i.c. bacteria are dependent on CD28-mediated costimulation."],["dc.identifier.doi","10.1007/s00430-010-0156-z"],["dc.identifier.isi","000280084000009"],["dc.identifier.pmid","20390297"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6752"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19366"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0300-8584"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","CD28 and IL-4: two heavyweights controlling the balance between immunity and inflammation"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Journal of Neuroimmunology"],["dc.bibliographiccitation.volume","178"],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Na, Shin-Young"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Huenig, Thomas"],["dc.date.accessioned","2018-11-07T09:20:44Z"],["dc.date.available","2018-11-07T09:20:44Z"],["dc.date.issued","2006"],["dc.format.extent","28"],["dc.identifier.isi","000241633100063"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28947"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.publisher.place","Amsterdam"],["dc.relation.eventlocation","Nagoya, JAPAN"],["dc.relation.issn","0165-5728"],["dc.title","Recruitment of regulatory T-cells to treat EAE"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","188"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","European Journal of Immunology"],["dc.bibliographiccitation.lastpage","193"],["dc.bibliographiccitation.volume","43"],["dc.contributor.author","Gogishvili, Tea"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Goebbels, Sandra"],["dc.contributor.author","Beer-Hammer, Sandra"],["dc.contributor.author","Pfeffer, Klaus"],["dc.contributor.author","Huenig, Thomas"],["dc.date.accessioned","2018-11-07T09:30:36Z"],["dc.date.available","2018-11-07T09:30:36Z"],["dc.date.issued","2013"],["dc.description.abstract","While the requirement for CD28 and its ligands for the generation and function of natural (n)Treg cells is well established, it has not been possible yet to investigate cell-intrinsic effects after interrupted CD28 expression. Here, we demonstrate a selective loss of Treg cells after disruption of the CD28 gene. The decline in Treg-cell number was accompanied by reduced homeostatic proliferation, probably due to lack of costimulation during self-antigen recognition, and by impaired Treg-cell function including downregulation of CTLA-4. The decline in Treg-cell number was unaffected by thymectomy or by the presence of CD28 expressing T cells within the same animal, indicating that impairment of peripheral homeostasis and function of nTreg cells by CD28 deletion is cell-intrinsic. In contrast, downregulation of CD25, the a chain of the IL-2R, did not occur in the presence of WT T cells, indicating that its expression does not depend on CD28 signals in cis."],["dc.identifier.doi","10.1002/eji.201242824"],["dc.identifier.isi","000313883200026"],["dc.identifier.pmid","23065717"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31340"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1521-4141"],["dc.relation.issn","0014-2980"],["dc.title","Cell-intrinsic and -extrinsic control of Treg-cell homeostasis and function revealed by induced CD28 deletion"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","721"],["dc.bibliographiccitation.journal","Frontiers in Immunology"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Uri, Anna"],["dc.contributor.author","Werner, Sandra"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Huenig, Thomas"],["dc.contributor.author","Kerkau, Thomas"],["dc.contributor.author","Beyersdorf, Niklas"],["dc.date.accessioned","2018-11-07T10:22:35Z"],["dc.date.available","2018-11-07T10:22:35Z"],["dc.date.issued","2017"],["dc.description.abstract","Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell plus T cell transplantation (allo-HSCT). In this study, we investigated the requirement for CD28 co-stimulation of donor CD4(+) conventional (CD4(+)CD25-Foxp3(-), Tconv) and regulatory (CD4(+)CD25(+)Foxp3(+), Treg) T cells in aGvHD using tamoxifen-inducible CD28 knockout (iCD28KO) or wild-type (wt) littermates as donors of CD4(+) Tconv and Treg. In the highly inflammatory C57BL/6 into BALB/c allo-HSCT transplantation model, CD28 depletion on donor CD4(+) Tconv reduced clinical signs of aGvHD, but did not significantly prolong survival of the recipient mice. Selective depletion of CD28 on donor Treg did not abrogate protection of recipient mice from aGvHD until about day 20 after allo-HSCT. Later, however, the pool of CD28-depleted Treg drastically declined as compared to wt Treg. Consequently, only wt, but not CD28-deficient, Treg were able to continuously suppress aGvHD and induce long-term survival of the recipient mice. To our knowledge, this is the first study that specifically evaluates the impact of CD28 expression on donor Treg in aGvHD. Moreover, the delayed kinetics of aGvHD lethality after transplantation of iCD28KO Treg provides a novel animal model for similar disease courses found in patients after allo-HSCT."],["dc.identifier.doi","10.3389/fimmu.2017.00721"],["dc.identifier.isi","000403949400002"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14983"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42303"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Frontiers Media Sa"],["dc.relation.issn","1664-3224"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Protection of Mice from Acute Graft-versus-Host Disease Requires CD28 Co-stimulation on Donor CD4(+) Foxp3(+) Regulatory T Cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]