Research output: Contribution to journal › Article › peer-review
Giovanni A. M. Povoleri, Sylvine Lalnunhlimi, Kathryn J. A. Steel, Shweta Agrawal, Aoife O'Byrne, Michael Ridley, Shahram Kordasti, Klaus S. Frederiksen, Ceri A. Roberts, Leonie S. Taams
Original language | English |
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Pages (from-to) | 445-458 |
Number of pages | 14 |
Journal | European Journal of Immunology |
Volume | 50 |
Issue number | 3 |
Early online date | 13 Nov 2019 |
DOIs | |
Accepted/In press | 12 Nov 2019 |
E-pub ahead of print | 13 Nov 2019 |
Published | Mar 2020 |
Additional links |
Anti-TNF treatment negatively regulates_POVOLERI_Accepted12November2019_GOLD VoR (CC BY)
Anti_TNF_treatment_negatively_regulates_POVOLERI_Accepted12November2019_GOLD_VoR_CC_BY_.pdf, 5.65 MB, application/pdf
Uploaded date:16 Dec 2019
Version:Accepted author manuscript
Licence:CC BY
TNF-blockade has shown clear therapeutic value in rheumatoid arthritis and other immune-mediated inflammatory diseases, however its mechanism of action is not fully elucidated. We investigated the effects of TNF-blockade on CD4 + T cell activation, maturation, and proliferation, and assessed whether TNF-inhibitors confer regulatory potential to CD4 + T cells. CyTOF and flow cytometry analysis revealed that in vitro treatment of human CD4 + T cells with the anti-TNF monoclonal antibody adalimumab promoted IL-10 expression in CD4 + T cells, whilst decreasing cellular activation. In line with this, analysis of gene expression profiling datasets of anti-TNF-treated IL-17 or IFN-γ-producing CD4 + T cells revealed changes in multiple pathways associated with cell cycle and proliferation. Kinetics experiments showed that anti-TNF treatment led to delayed, rather than impaired T-cell activation and maturation. Whilst anti-TNF-treated CD4 + T cells displayed some hyporesponsiveness upon restimulation, they did not acquire enhanced capacity to suppress T-cell responses or modulate monocyte phenotype. These cells however displayed a reduced ability to induce IL-6 and IL-8 production by synovial fibroblasts. Together, these data indicate that anti-TNF treatment delays human CD4 + T-cell activation, maturation, and proliferation, and this reduced activation state may impair their ability to activate stromal cells.
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