Figure 6. Abatacept blunts cardiac dysfunction by suppressing the immune response.

Schematic cartoon of the mechanism of action of abatacept in heart failure. In pathological hypertrophy, T cells are activated (through their TCR) and receive costimulation via CD28 from CD80/CD86-expressing antigen presenting cells (macrophages, B cells, dendritic cells). The full activation of T cells, identified by high levels of CD25, enhances the chronicity of the cardiac inflammatory response. This also involves the proinflammatory action of cardiac macrophages. As a result, there is increased cardiomyocyte apoptosis, fibrosis and reduced heart functionality. During abatacept treatment, the drug blocks CD80/CD86-mediated costimulation by macrophages and B cells, leading to inhibition of T cell activation, proliferation and/or infiltration. The effects on macrophages (which may be both direct and indirect) lead to lower maturation and infiltration. Direct effects on B cells lead to production of anti-inflammatory cytokine IL-10, which may also be produced to a lesser extent by T cells. As a consequence of the effect on T cells, B cells and macrophages, the progression of cardiac pathology is blocked, even if the drug is administered at a late stage. The protective effect is dependent on IL-10 presence.