Background: Alemtuzumab (ALM) effectively prevents multiple sclerosis (MS) relapses. It causes lymphocytic depletion with subsequent enhancement of T-regulatory cell population. Direct administration of ALM to T-cells causes cytolysis. However, the T-cells may be indirectly affected by myeloid cells, which are resistant to ALM cytotoxicity.
Does ALM modulate monocytes? Does the cross-talk between exposed monocytes and lymphocytes result in anti-inflammatory effects?
Methods: CD14+ monocytes of 10 healthy controls and 10 MS (treatment naïve) patients were isolated from peripheral blood mononuclear cells (PBMCs), exposed to ALM and reintroduced to PBMCs depleted from CD14+ cells. After treatment, macrophage profile and T-cells markers were measured.
Results: ALM promoted M2 anti-inflammatory phenotype, noted by increased percentage of CD23+, CD83+ and CD163+ cells. CD23+ cells were the most prominently upregulated (7-fold, p=0.0002). Observed effect was larger in MS patients compared to healthy subjects. The exposed macrophages increased the proportion of T-regulatory cells, without affecting T-effector cells. Neutralization of monocytic CD23 reversed the effect on T-regulatory cells.
Conclusions: ALM enabled monocytes’ conversion towards anti-inflammatory macrophages, which in turn promoted T-regulatory enhancement, in CD23 dependent manner. These findings suggest an ALM mechanism of action, which may explain some aspects of the MS pathogenesis.