Anti-TNF treatment negatively regulates human CD4+ T-cell activation and maturation in vitro, but does not confer an anergic or suppressive phenotype.
Eur J Immunol
; 50(3): 445-458, 2020 03.
Article
em En
| MEDLINE
| ID: mdl-31722123
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ativação Linfocitária
/
Linfócitos T CD4-Positivos
/
Diferenciação Celular
/
Adalimumab
/
Anti-Inflamatórios
Limite:
Humans
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Reino Unido