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Anti‐TNF treatment negatively regulates human CD4 + T‐cell activation and maturation in vitro, but does not confer an anergic or suppressive phenotype
- Source :
- European Journal of Immunology, Povoleri, G A M, Lalnunhlimi, S, Steel, K J A, Agrawal, S, O'Byrne, A, Ridley, M, Kordasti, S, Frederiksen, K S, Roberts, C A & Taams, L S 2020, ' Anti-TNF treatment negatively regulates human CD4+ T-cell activation and maturation in vitro, but does not confer an anergic or suppressive phenotype ', European Journal of Immunology, vol. 50, no. 3, pp. 445-458 . https://doi.org/10.1002/eji.201948190
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- 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.<br />Through deep phenotyping using CyTOF and functional assays we have shown that TNF inhibition using adalimumab altered the phenotype and function of multiple populations of human CD4+ T‐cells, leading to an overall decreased pro‐inflammatory potential. These results provide insight into the anti‐TNF mechanism of action in human CD4+ T‐cells.
- Subjects :
- CD4-Positive T-Lymphocytes
0301 basic medicine
Immunomodulation and immune therapies
Stromal cell
T cell
interleukin-10
Immunology
Anti-Inflammatory Agents
Biology
Lymphocyte Activation
Flow cytometry
03 medical and health sciences
CD4+ T cells
0302 clinical medicine
interleukin‐10
adalimumab
medicine
Humans
Immunology and Allergy
Basic
Cells, Cultured
Cell Proliferation
Clonal Anergy
medicine.diagnostic_test
Tumor Necrosis Factor-alpha
Monocyte
Adalimumab
Cell Differentiation
Cell cycle
In vitro
3. Good health
Cell biology
Interleukin 10
Phenotype
030104 developmental biology
medicine.anatomical_structure
Research Article|Basic
Tumor necrosis factor alpha
CyTOF
CD4 T cells
Research Article
TNF inhibitor
030215 immunology
Subjects
Details
- ISSN :
- 15214141 and 00142980
- Volume :
- 50
- Database :
- OpenAIRE
- Journal :
- European Journal of Immunology
- Accession number :
- edsair.doi.dedup.....3811cf191a928fdf139aa61c202c615b