Show simple item record

dc.contributor.authorGunnlaugsdottir, B
dc.contributor.authorSkaftadottir, I
dc.contributor.authorLudviksson, B R
dc.date.accessioned2008-12-19T15:21:34Z
dc.date.available2008-12-19T15:21:34Z
dc.date.issued2008-12-01
dc.date.submitted2008-12-19
dc.identifier.citationScand. J. Immunol. 2008, 68(6):624-34en
dc.identifier.issn0300-9475
dc.identifier.pmid19000096
dc.identifier.doi10.1111/j.1365-3083.2008.02181.x
dc.identifier.urihttp://hdl.handle.net/2336/46775
dc.descriptionNeðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/Openen
dc.description.abstractTumour necrosis factor alpha (TNFalpha) inhibitors are widely used successfully as immunomodulatory agents in various autoimmune diseases. They primarily target the direct pro-inflammatory effect of TNFalpha. They have also been found to be critical for T-cell viability and activation. In this study we evaluated the effect of infliximab treatment under different in vitro stimulatory conditions of naive human cord blood T-cells and adult peripheral blood mononuclear cells (PBMC). PBMC and negatively selected cord blood naive human T-cells were stimulated with alphaCD3 with or without alphaCD28 co-stimulation. The role of in vitro infliximab treatment was evaluated in relation to transforming growth factor-beta1 (TGF-beta1) under the above different stimulatory conditions. Anti-TNFalpha treatment with infliximab significantly suppressed proliferation of adult and cord blood T-cells (P < 0.013) during suboptimal stimulatory conditions. Infliximab prevented division of naive CD4+ and CD8+ T-cells and consequently also activation induced cell death, which was induced after three cell divisions. Interleukin (IL)-2 secretion was significantly decreased during infliximab treatment of suboptimally stimulated T-cells (P < 0.05) while TGF-beta1 levels were unchanged. Strikingly, the anti-proliferative effect of infliximab was overcome by the administration of anti-TGF-beta1 or by the addition of exogenous IL-2. Interestingly, CD28 mediated co-stimulation restored the proliferative response in a dose-responsive manner during infliximab treatment. Finally, exogenous TNFalpha administration during suboptimal stimulation reduced the inhibitory effect of TGF-beta1 upon proliferation (P < 0.03). These results demonstrate that anti-TNFalpha treatment is primarily working upon T cells under low stimulatory conditions and probably through TGF-beta1.
dc.language.isoenen
dc.publisherBlackwell Scientific Publicationsen
dc.relation.urlhttp://www3.interscience.wiley.com/journal/121495296/abstracten
dc.subject.meshInterleukin-2en
dc.subject.meshAntibodies, Monoclonalen
dc.subject.meshTransforming Growth Factor beta1en
dc.subject.meshTumor Necrosis Factor-alphaen
dc.titleNaive human T-cells become non-responsive towards anti-TNFalpha (infliximab) treatment in vitro if co-stimulated through CD28en
dc.typeArticleen
dc.identifier.eissn1365-3083
dc.contributor.departmentDepartment of Immunology, Landspitali-University Hospital, Reykjavik, Iceland.en
dc.identifier.journalScandinavian journal of immunologyen
html.description.abstractTumour necrosis factor alpha (TNFalpha) inhibitors are widely used successfully as immunomodulatory agents in various autoimmune diseases. They primarily target the direct pro-inflammatory effect of TNFalpha. They have also been found to be critical for T-cell viability and activation. In this study we evaluated the effect of infliximab treatment under different in vitro stimulatory conditions of naive human cord blood T-cells and adult peripheral blood mononuclear cells (PBMC). PBMC and negatively selected cord blood naive human T-cells were stimulated with alphaCD3 with or without alphaCD28 co-stimulation. The role of in vitro infliximab treatment was evaluated in relation to transforming growth factor-beta1 (TGF-beta1) under the above different stimulatory conditions. Anti-TNFalpha treatment with infliximab significantly suppressed proliferation of adult and cord blood T-cells (P < 0.013) during suboptimal stimulatory conditions. Infliximab prevented division of naive CD4+ and CD8+ T-cells and consequently also activation induced cell death, which was induced after three cell divisions. Interleukin (IL)-2 secretion was significantly decreased during infliximab treatment of suboptimally stimulated T-cells (P < 0.05) while TGF-beta1 levels were unchanged. Strikingly, the anti-proliferative effect of infliximab was overcome by the administration of anti-TGF-beta1 or by the addition of exogenous IL-2. Interestingly, CD28 mediated co-stimulation restored the proliferative response in a dose-responsive manner during infliximab treatment. Finally, exogenous TNFalpha administration during suboptimal stimulation reduced the inhibitory effect of TGF-beta1 upon proliferation (P < 0.03). These results demonstrate that anti-TNFalpha treatment is primarily working upon T cells under low stimulatory conditions and probably through TGF-beta1.


This item appears in the following Collection(s)

Show simple item record