Gemcitabine directly inhibits effector CD4 T cell activation and prevents experimental autoimmune encephalomyelitis

Pro-inflammatory T cells are critical to the pathogenesis of multiple sclerosis (MS). We investigated the potential for the anti-proliferative, pro-apoptotic drug gemcitabine to affect development of MS-relevant effector T_H1, T_H17, and Treg cells. Gemcitabine directly suppressed proliferation, activation, and induced apoptosis of all effector subsets in subtype and dose-dependent fashion. This drug also prevented development of disease in the MS model experimental autoimmune encephalomyelitis (EAE) and significantly reduced the abundance of T_H1 and T_H17 cells. Our results indicate that pathogenic CD4⁺ T cells may be viable targets by gemcitabine for therapeutic benefit in MS.