The effect of abatacept on T-cell activation is not long-lived in vivo .
Larissa Camargo da RosaHannah E ScalesRobert A BensonJames M BrewerIain B McInnesPaul GarsidePublished in: Discovery immunology (2024)
Abatacept, a co-stimulatory blocker comprising the extracellular portion of human CTLA-4 linked to the Fc region of IgG1, is approved for the treatment of rheumatoid arthritis. By impairing the interaction between CD28 on T cells and CD80/CD86 on APCs, its mechanisms of action include the suppression of follicular T helper cells (preventing the breach of self-tolerance in B cells), inhibition of cell cycle progression holding T cells in a state described as 'induced naïve' and reduction in DC conditioning. However, less is known about how long these inhibitory effects might last, which is a critical question for therapeutic use in patients. Herein, employing a murine model of OVA-induced DTH, we demonstrate that the effect of abatacept is short-lived in vivo and that the inhibitory effects diminish markedly when treatment is ceased.
Keyphrases
- rheumatoid arthritis
- cell cycle
- high glucose
- endothelial cells
- disease activity
- cell proliferation
- ejection fraction
- dendritic cells
- rheumatoid arthritis patients
- diabetic rats
- newly diagnosed
- induced apoptosis
- immune response
- prognostic factors
- systemic lupus erythematosus
- patient reported outcomes
- systemic sclerosis
- smoking cessation
- stress induced
- pluripotent stem cells